Skip to main content

Advertisement

Log in

Navigating the diverse immune landscapes of psoriatic arthritis

  • Review
  • Published:
Seminars in Immunopathology Aims and scope Submit manuscript

Abstract

The goal of remission in psoriatic arthritis (PsA) has remained elusive despite the influx of a range of new therapies over the last 20 years. In contrast, therapeutic responses to agents that inhibit IL-23 or IL-17 have demonstrated impressive efficacy in psoriasis. In part, the divergent responses in these two disorders are likely related to the heterogeneity of tissue involvement in PsA and the interplay of multiple different cell populations and molecular pathways. In this narrative review, we will examine the plasticity of the immune response in PsA from the perspective of the Th17 cell and monocyte and discuss recent findings regarding the importance of CD8+ T resident cells in disease pathogenesis. We will then examine the effects of cytokines on epithelial cell and stromal populations and finally discuss new data regarding immune cell and tissue resident cell cross-talk in entheses and bone. Lastly, the potential therapeutic targets that have emerged from these investigations will be discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ritchlin C, Scher JU (2019) Strategies to improve outcomes in psoriatic arthritis. Curr Rheumatol Rep 21(12):72. https://doi.org/10.1007/s11926-019-0876-z

    Article  PubMed  Google Scholar 

  2. Kavanaugh AF, Ritchlin CT, Committee GTG (2006) Systematic review of treatments for psoriatic arthritis: an evidence based approach and basis for treatment guidelines. J Rheumatol 33(7):1417–1421

    PubMed  Google Scholar 

  3. Ogdie A, Schwartzman S, Husni ME (2015) Recognizing and managing comorbidities in psoriatic arthritis. Curr Opin Rheumatol 27(2):118–126. https://doi.org/10.1097/BOR.0000000000000152

    Article  PubMed  Google Scholar 

  4. Gravallese EM, Schett G (2018) Effects of the IL-23-IL-17 pathway on bone in spondyloarthritis. Nat Rev Rheumatol 14(11):631–640. https://doi.org/10.1038/s41584-018-0091-8

    Article  CAS  PubMed  Google Scholar 

  5. Ritchlin CT, Colbert RA, Gladman DD (2017) Psoriatic arthritis. The New England journal of medicine 376(10):957–970. https://doi.org/10.1056/NEJMra1505557

    Article  PubMed  Google Scholar 

  6. Lubberts E (2015) The IL-23-IL-17 axis in inflammatory arthritis. Nat Rev Rheumatol 11(10):562. https://doi.org/10.1038/nrrheum.2015.128

    Article  PubMed  Google Scholar 

  7. Stadhouders R, Lubberts E, Hendriks RW (2018) A cellular and molecular view of T helper 17 cell plasticity in autoimmunity. J Autoimmun 87:1–15. https://doi.org/10.1016/j.jaut.2017.12.007

    Article  CAS  PubMed  Google Scholar 

  8. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136(7):2348–2357

    CAS  PubMed  Google Scholar 

  9. Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, Lucian L, To W, Kwan S, Churakova T, Zurawski S, Wiekowski M, Lira SA, Gorman D, Kastelein RA, Sedgwick JD (2003) Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421(6924):744–748. https://doi.org/10.1038/nature01355

    Article  CAS  PubMed  Google Scholar 

  10. Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA (2000) Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13(5):715–725. https://doi.org/10.1016/s1074-7613(00)00070-4

    Article  CAS  PubMed  Google Scholar 

  11. Meyer Zu Horste G, Wu C, Wang C, Cong L, Pawlak M, Lee Y, Elyaman W, Xiao S, Regev A, Kuchroo VK (2016) RBPJ controls development of pathogenic Th17 cells by regulating IL-23 receptor expression. Cell Rep 16(2):392–404. https://doi.org/10.1016/j.celrep.2016.05.088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lee Y, Awasthi A, Yosef N, Quintana FJ, Xiao S, Peters A, Wu C, Kleinewietfeld M, Kunder S, Hafler DA, Sobel RA, Regev A, Kuchroo VK (2012) Induction and molecular signature of pathogenic TH17 cells. Nat Immunol 13(10):991–999. https://doi.org/10.1038/ni.2416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Burkett PR, Meyer zu Horste G, Kuchroo VK (2015) Pouring fuel on the fire: Th17 cells, the environment, and autoimmunity. J Clin Invest 125(6):2211–2219. https://doi.org/10.1172/JCI78085

    Article  PubMed  PubMed Central  Google Scholar 

  14. Miossec P, Korn T, Kuchroo VK (2009) Interleukin-17 and type 17 helper T cells. New England Journal of Medicine 361(9):888–898

    Article  CAS  PubMed  Google Scholar 

  15. Omenetti S, Bussi C, Metidji A, Iseppon A, Lee S, Tolaini M, Li Y, Kelly G, Chakravarty P, Shoaie S, Gutierrez MG, Stockinger B (2019) The intestine harbors functionally distinct homeostatic tissue-resident and inflammatory Th17 cells. Immunity 51(1):77–89 e76. https://doi.org/10.1016/j.immuni.2019.05.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Das A, Sinha M, Datta S, Abas M, Chaffee S, Sen CK, Roy S (2015) Monocyte and macrophage plasticity in tissue repair and regeneration. Am J Pathol 185(10):2596–2606. https://doi.org/10.1016/j.ajpath.2015.06.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Mensah K, Mathian A, Xing L, Ritchlin C, Schwarz E (2009) Nonerosive arthritis is mediated by IFN-a stimulated monocyte differentiation that is nonpermissive of osteoclastogenesis. Arthritis and Rheumatism (manuscript submitted)

  18. Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K (2010) Development of monocytes, macrophages, and dendritic cells. Science 327(5966):656–661. https://doi.org/10.1126/science.1178331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Miossec P, Kolls JK (2012) Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov 11(10):763–776. https://doi.org/10.1038/nrd3794

    Article  CAS  PubMed  Google Scholar 

  20. Proulx ST, Kwok E, You Z, Papuga MO, Beck CA, Shealy DJ, Calvi LM, Ritchlin CT, Awad HA, Boyce BF, Xing L, Schwarz EM (2008) Elucidating bone marrow edema and myelopoiesis in murine arthritis using contrast-enhanced magnetic resonance imaging. Arthritis Rheum 58(7):2019–2029. https://doi.org/10.1002/art.23546

    Article  PubMed  PubMed Central  Google Scholar 

  21. Adamopoulos IE, Suzuki E, Chao CC, Gorman D, Adda S, Maverakis E, Zarbalis K, Geissler R, Asio A, Blumenschein WM, McClanahan T, De Waal Malefyt R, Gershwin ME, Bowman EP (2015) IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis. Ann Rheum Dis 74 (6):1284-1292. https://doi.org/10.1136/annrheumdis-2013-204782

  22. Adamopoulos IE, Tessmer M, Chao CC, Adda S, Gorman D, Petro M, Chou CC, Pierce RH, Yao W, Lane NE, Laface D, Bowman EP (2011) IL-23 is critical for induction of arthritis, osteoclast formation, and maintenance of bone mass. J Immunol 187(2):951–959. https://doi.org/10.4049/jimmunol.1003986

    Article  CAS  PubMed  Google Scholar 

  23. Zaba LC, Krueger JG, Lowes MA (2009) Resident and "inflammatory" dendritic cells in human skin. J Invest Dermatol 129(2):302–308. https://doi.org/10.1038/jid.2008.225

    Article  CAS  PubMed  Google Scholar 

  24. Malissen B, Tamoutounour S, Henri S (2014) The origins and functions of dendritic cells and macrophages in the skin. Nat Rev Immunol 14(6):417–428. https://doi.org/10.1038/nri3683

    Article  CAS  PubMed  Google Scholar 

  25. Otsuka M, Egawa G, Kabashima K (2018) Uncovering the mysteries of Langerhans cells, inflammatory dendritic epidermal cells, and monocyte-derived Langerhans cell-like cells in the epidermis. Front Immunol 9:1768. https://doi.org/10.3389/fimmu.2018.01768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Cumberbatch M, Dearman RJ, Kimber I (1997) Langerhans cells require signals from both tumour necrosis factor-alpha and interleukin-1 beta for migration. Immunology 92(3):388–395. https://doi.org/10.1046/j.1365-2567.1997.00360.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Singh TP, Zhang HH, Borek I, Wolf P, Hedrick MN, Singh SP, Kelsall BL, Clausen BE, Farber JM (2016) Monocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation. Nat Commun 7:13581. https://doi.org/10.1038/ncomms13581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Belge KU, Dayyani F, Horelt A, Siedlar M, Frankenberger M, Frankenberger B, Espevik T, Ziegler-Heitbrock L (2002) The proinflammatory CD14+CD16+DR++ monocytes are a major source of TNF. J Immunol 168(7):3536–3542

    Article  CAS  PubMed  Google Scholar 

  29. Chiu YG, Shao T, Feng C, Mensah KA, Thullen M, Schwarz EM, Ritchlin CT (2010) CD16 (FcRgammaIII) as a potential marker of osteoclast precursors in psoriatic arthritis. Arthritis Res Ther 12(1):R14. https://doi.org/10.1186/ar2915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Matt P, Lindqvist U, Kleinau S (2015) Up-regulation of CD64-expressing monocytes with impaired FcgammaR function reflects disease activity in polyarticular psoriatic arthritis. Scand J Rheumatol 44(6):464–473. https://doi.org/10.3109/03009742.2015.1020864

    Article  CAS  PubMed  Google Scholar 

  31. Aochi S, Tsuji K, Sakaguchi M, Huh N, Tsuda T, Yamanishi K, Komine M, Iwatsuki K (2011) Markedly elevated serum levels of calcium-binding S100A8/A9 proteins in psoriatic arthritis are due to activated monocytes/macrophages. J Am Acad Dermatol 64(5):879–887. https://doi.org/10.1016/j.jaad.2010.02.049

    Article  CAS  PubMed  Google Scholar 

  32. Ritchlin CT, Haas-Smith SA, Li P, Hicks DG, Schwarz EM (2003) Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest 111(6):821–831. https://doi.org/10.1172/JCI16069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. McGonagle D, Marzo-Ortega H, O'Connor P, Gibbon W, Hawkey P, Henshaw K, Emery P (2002) Histological assessment of the early enthesitis lesion in spondyloarthropathy. Ann Rheum Dis 61(6):534–537. https://doi.org/10.1136/ard.61.6.534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Culemann S, Gruneboom A, Nicolas-Avila JA, Weidner D, Lammle KF, Rothe T, Quintana JA, Kirchner P, Krljanac B, Eberhardt M, Ferrazzi F, Kretzschmar E, Schicht M, Fischer K, Gelse K, Faas M, Pfeifle R, Ackermann JA, Pachowsky M, Renner N, Simon D, Haseloff RF, Ekici AB, Bauerle T, Blasig IE, Vera J, Voehringer D, Kleyer A, Paulsen F, Schett G, Hidalgo A, Kronke G (2019) Locally renewing resident synovial macrophages provide a protective barrier for the joint. Nature 572(7771):670–675. https://doi.org/10.1038/s41586-019-1471-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. von Andrian UH, Mackay CR (2000) T-cell function and migration. Two sides of the same coin. The New England journal of medicine 343(14):1020–1034. https://doi.org/10.1056/NEJM200010053431407

    Article  Google Scholar 

  36. Boyman O, Hefti HP, Conrad C, Nickoloff BJ, Suter M, Nestle FO (2004) Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and tumor necrosis factor-alpha. J Exp Med 199(5):731–736. https://doi.org/10.1084/jem.20031482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Clark RA, Chong B, Mirchandani N, Brinster NK, Yamanaka K, Dowgiert RK, Kupper TS (2006) The vast majority of CLA+ T cells are resident in normal skin. J Immunol 176(7):4431–4439. https://doi.org/10.4049/jimmunol.176.7.4431

    Article  CAS  PubMed  Google Scholar 

  38. Cheuk S, Wiken M, Blomqvist L, Nylen S, Talme T, Stahle M, Eidsmo L (2014) Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis. J Immunol 192(7):3111–3120. https://doi.org/10.4049/jimmunol.1302313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Matos TR, O'Malley JT, Lowry EL, Hamm D, Kirsch IR, Robins HS, Kupper TS, Krueger JG, Clark RA (2017) Clinically resolved psoriatic lesions contain psoriasis-specific IL-17-producing alphabeta T cell clones. J Clin Invest 127(11):4031–4041. https://doi.org/10.1172/JCI93396

    Article  PubMed  PubMed Central  Google Scholar 

  40. Masopust D, Soerens AG (2019) Tissue-resident T cells and other resident leukocytes. Annu Rev Immunol 37:521–546. https://doi.org/10.1146/annurev-immunol-042617-053214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Schenkel JM, Masopust D (2014) Tissue-resident memory T cells. Immunity 41(6):886–897. https://doi.org/10.1016/j.immuni.2014.12.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Watanabe R, Gehad A, Yang C, Scott LL, Teague JE, Schlapbach C, Elco CP, Huang V, Matos TR, Kupper TS, Clark RA (2015) Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells. Sci Transl Med 7(279):279ra239. https://doi.org/10.1126/scitranslmed.3010302

    Article  CAS  Google Scholar 

  43. Petrelli A, van Wijk F (2016) CD8(+) T cells in human autoimmune arthritis: the unusual suspects. Nat Rev Rheumatol 12 (7):421-428. https://doi.org/10.1038/nrrheum.2016.74

  44. Menon B, Gullick NJ, Walter GJ, Rajasekhar M, Garrood T, Evans HG, Taams LS, Kirkham BW (2014) Interleukin-17+CD8+ T cells are enriched in the joints of patients with psoriatic arthritis and correlate with disease activity and joint damage progression. Arthritis Rheumatol 66(5):1272–1281. https://doi.org/10.1002/art.38376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Wade SM, Canavan M, McGarry T, Low C, Wade SC, Mullan RH, Veale DJ, Fearon U (2019) Association of synovial tissue polyfunctional T-cells with DAPSA in psoriatic arthritis. Ann Rheum Dis 78(3):350–354. https://doi.org/10.1136/annrheumdis-2018-214138

    Article  CAS  PubMed  Google Scholar 

  46. Raychaudhuri SK, Abria C, Raychaudhuri SP (2019) Polyfunctional TEM cells in psoriatic arthritis synovium skewed towards Th17 cells. Ann Rheum Dis. https://doi.org/10.1136/annrheumdis-2019-216658

  47. Steel KJA, Srenathan U, Ridley M, Durham LE, Wu SY, Ryan SE, Hughes CD, Chan E, Kirkham BW, Taams LS (2020) Polyfunctional, proinflammatory, tissue-resident memory phenotype and function of synovial interleukin-17A+CD8+ T cells in psoriatic arthritis. Arthritis Rheumatol 72(3):435–447. https://doi.org/10.1002/art.41156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Croft AP, Campos J, Jansen K, Turner JD, Marshall J, Attar M, Savary L, Wehmeyer C, Naylor AJ, Kemble S, Begum J, Durholz K, Perlman H, Barone F, McGettrick HM, Fearon DT, Wei K, Raychaudhuri S, Korsunsky I, Brenner MB, Coles M, Sansom SN, Filer A, Buckley CD (2019) Distinct fibroblast subsets drive inflammation and damage in arthritis. Nature 570(7760):246–251. https://doi.org/10.1038/s41586-019-1263-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Donlin LT, Rao DA, Wei K, Slowikowski K, McGeachy MJ, Turner JD, Meednu N, Mizoguchi F, Gutierrez-Arcelus M, Lieb DJ, Keegan J, Muskat K, Hillman J, Rozo C, Ricker E, Eisenhaure TM, Li S, Browne EP, Chicoine A, Sutherby D, Noma A, Nusbaum C, Kelly S, Pernis AB, Ivashkiv LB, Goodman SM, Robinson WH, Utz PJ, Lederer JA, Gravallese EM, Boyce BF, Hacohen N, Pitzalis C, Gregersen PK, Firestein GS, Raychaudhuri S, Moreland LW, Holers VM, Bykerk VP, Filer A, Boyle DL, Brenner MB, Anolik JH (2018) Methods for high-dimensional analysis of cells dissociated from cryopreserved synovial tissue. Arthritis Res Ther 20(1):139. https://doi.org/10.1186/s13075-018-1631-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Rao DA, Gurish MF, Marshall JL, Slowikowski K, Fonseka CY, Liu Y, Donlin LT, Henderson LA, Wei K, Mizoguchi F, Teslovich NC, Weinblatt ME, Massarotti EM, Coblyn JS, Helfgott SM, Lee YC, Todd DJ, Bykerk VP, Goodman SM, Pernis AB, Ivashkiv LB, Karlson EW, Nigrovic PA, Filer A, Buckley CD, Lederer JA, Raychaudhuri S, Brenner MB (2017) Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis. Nature 542(7639):110–114. https://doi.org/10.1038/nature20810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Zhang Z, Wen H, Yang X, Zhang K, He B, Zhang X, Kong L (2019) Stimuli and relevant signaling cascades for NFATc1 in bone cell homeostasis: friend or foe? Curr Stem Cell Res Ther 14(3):239–243. https://doi.org/10.2174/1574888X14666181205122729

    Article  CAS  PubMed  Google Scholar 

  52. Penkava F, Velasco-Herrera MDC, Young MD, Yager N, Nwosu LN, Pratt AG, Lara AL, Guzzo C, Maroof A, Mamanova L, Cole S, Efremova M, Simone D, Filer A, Brown CC, Croxford AL, Isaacs JD, Teichmann S, Bowness P, Behjati S, Hussein Al-Mossawi M (2020) Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis. Nat Commun 11(1):4767. https://doi.org/10.1038/s41467-020-18513-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Yuan Y, Qiu J, Lin ZT, Li W, Haley C, Mui UN, Ning J, Tyring SK, Wu T (2019) Identification of novel autoantibodies associated with psoriatic arthritis. Arthritis Rheumatol 71(6):941–951. https://doi.org/10.1002/art.40830

    Article  CAS  PubMed  Google Scholar 

  54. Krueger JG, Brunner PM (2018) Interleukin-17 alters the biology of many cell types involved in the genesis of psoriasis, systemic inflammation and associated comorbidities. Exp Dermatol 27(2):115–123. https://doi.org/10.1111/exd.13467

    Article  CAS  PubMed  Google Scholar 

  55. Ho YJ, Anaparthy N, Molik D, Mathew G, Aicher T, Patel A, Hicks J, Hammell MG (2018) Single-cell RNA-seq analysis identifies markers of resistance to targeted BRAF inhibitors in melanoma cell populations. Genome Res 28(9):1353–1363. https://doi.org/10.1101/gr.234062.117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Hartupee J, Liu C, Novotny M, Li X, Hamilton T (2007) IL-17 enhances chemokine gene expression through mRNA stabilization. J Immunol 179(6):4135–4141. https://doi.org/10.4049/jimmunol.179.6.4135

    Article  CAS  PubMed  Google Scholar 

  57. Henness S, Johnson CK, Ge Q, Armour CL, Hughes JM, Ammit AJ (2004) IL-17A augments TNF-alpha-induced IL-6 expression in airway smooth muscle by enhancing mRNA stability. J Allergy Clin Immunol 114(4):958–964. https://doi.org/10.1016/j.jaci.2004.06.023

    Article  CAS  PubMed  Google Scholar 

  58. Chabaud M, Miossec P (2001) The combination of tumor necrosis factor alpha blockade with interleukin-1 and interleukin-17 blockade is more effective for controlling synovial inflammation and bone resorption in an ex vivo model. Arthritis Rheum 44(6):1293–1303. https://doi.org/10.1002/1529-0131(200106)44:6<1293::AID-ART221>3.0.CO;2-T

    Article  CAS  PubMed  Google Scholar 

  59. Alzabin S, Abraham SM, Taher TE, Palfreeman A, Hull D, McNamee K, Jawad A, Pathan E, Kinderlerer A, Taylor PC, Williams R, Mageed R (2012) Incomplete response of inflammatory arthritis to TNFalpha blockade is associated with the Th17 pathway. Ann Rheum Dis 71(10):1741–1748. https://doi.org/10.1136/annrheumdis-2011-201024

    Article  CAS  PubMed  Google Scholar 

  60. Belasco J, Louie JS, Gulati N, Wei N, Nograles K, Fuentes-Duculan J, Mitsui H, Suarez-Farinas M, Krueger JG (2015) Comparative genomic profiling of synovium versus skin lesions in psoriatic arthritis. Arthritis Rheumatol 67(4):934–944. https://doi.org/10.1002/art.38995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Ni X, Lai Y (2020) Keratinocyte: a trigger or an executor of psoriasis? J Leukoc Biol 108(2):485–491. https://doi.org/10.1002/JLB.5MR0120-439R

    Article  CAS  PubMed  Google Scholar 

  62. Albanesi C, Madonna S, Gisondi P, Girolomoni G (2018) The interplay between keratinocytes and immune cells in the pathogenesis of psoriasis. Front Immunol 9:1549. https://doi.org/10.3389/fimmu.2018.01549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Eyerich S, Eyerich K, Pennino D, Carbone T, Nasorri F, Pallotta S, Cianfarani F, Odorisio T, Traidl-Hoffmann C, Behrendt H, Durham SR, Schmidt-Weber CB, Cavani A (2009) Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J Clin Invest 119(12):3573–3585. https://doi.org/10.1172/JCI40202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Chiricozzi A, Guttman-Yassky E, Suarez-Farinas M, Nograles KE, Tian S, Cardinale I, Chimenti S, Krueger JG (2011) Integrative responses to IL-17 and TNF-alpha in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis. J Invest Dermatol 131(3):677–687. https://doi.org/10.1038/jid.2010.340

    Article  CAS  PubMed  Google Scholar 

  65. Boniface K, Bernard FX, Garcia M, Gurney AL, Lecron JC, Morel F (2005) IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes. J Immunol 174(6):3695–3702. https://doi.org/10.4049/jimmunol.174.6.3695

    Article  CAS  PubMed  Google Scholar 

  66. Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R (2004) IL-22 increases the innate immunity of tissues. Immunity 21(2):241–254. https://doi.org/10.1016/j.immuni.2004.07.007

    Article  CAS  PubMed  Google Scholar 

  67. Wolk K, Witte E, Wallace E, Docke WD, Kunz S, Asadullah K, Volk HD, Sterry W, Sabat R (2006) IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur J Immunol 36(5):1309–1323. https://doi.org/10.1002/eji.200535503

    Article  CAS  PubMed  Google Scholar 

  68. Gudjonsson JE, Johnston A, Ellis CN (2012) Novel systemic drugs under investigation for the treatment of psoriasis. J Am Acad Dermatol 67(1):139–147. https://doi.org/10.1016/j.jaad.2011.06.037

    Article  CAS  PubMed  Google Scholar 

  69. Armaka M, Apostolaki M, Jacques P, Kontoyiannis DL, Elewaut D, Kollias G (2008) Mesenchymal cell targeting by TNF as a common pathogenic principle in chronic inflammatory joint and intestinal diseases. J Exp Med 205(2):331–337. https://doi.org/10.1084/jem.20070906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Lubberts E, Schwarzenberger P, Huang W, Schurr JR, Peschon JJ, van den Berg WB, Kolls JK (2005) Requirement of IL-17 receptor signaling in radiation-resistant cells in the joint for full progression of destructive synovitis. J Immunol 175 (5):3360-3368. https://doi.org/10.4049/jimmunol.175.5.3360

  71. Fossiez F, Djossou O, Chomarat P, Flores-Romo L, Ait-Yahia S, Maat C, Pin JJ, Garrone P, Garcia E, Saeland S, Blanchard D, Gaillard C, Das Mahapatra B, Rouvier E, Golstein P, Banchereau J, Lebecque S (1996) T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med 183(6):2593–2603. https://doi.org/10.1084/jem.183.6.2593

    Article  CAS  PubMed  Google Scholar 

  72. van Hamburg JP, Corneth OB, Paulissen SM, Davelaar N, Asmawidjaja PS, Mus AM, Lubberts E (2013) IL-17/Th17 mediated synovial inflammation is IL-22 independent. Ann Rheum Dis 72(10):1700–1707. https://doi.org/10.1136/annrheumdis-2012-202373

    Article  CAS  PubMed  Google Scholar 

  73. Moran EM, Mullan R, McCormick J, Connolly M, Sullivan O, Fitzgerald O, Bresnihan B, Veale DJ, Fearon U (2009) Human rheumatoid arthritis tissue production of IL-17A drives matrix and cartilage degradation: synergy with tumour necrosis factor-alpha, Oncostatin M and response to biologic therapies. Arthritis Res Ther 11(4):R113. https://doi.org/10.1186/ar2772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Eljaafari A, Tartelin ML, Aissaoui H, Chevrel G, Osta B, Lavocat F, Miossec P (2012) Bone marrow-derived and synovium-derived mesenchymal cells promote Th17 cell expansion and activation through caspase 1 activation: contribution to the chronicity of rheumatoid arthritis. Arthritis Rheum 64(7):2147–2157. https://doi.org/10.1002/art.34391

    Article  CAS  PubMed  Google Scholar 

  75. Kim KW, Kim HR, Park JY, Park JS, Oh HJ, Woo YJ, Park MK, Cho ML, Lee SH (2012) Interleukin-22 promotes osteoclastogenesis in rheumatoid arthritis through induction of RANKL in human synovial fibroblasts. Arthritis Rheum 64(4):1015–1023. https://doi.org/10.1002/art.33446

    Article  CAS  PubMed  Google Scholar 

  76. Li X, Kim KW, Cho ML, Ju JH, Kang CM, Oh HJ, Min JK, Lee SH, Park SH, Kim HY (2010) IL-23 induces receptor activator of NF-kappaB ligand expression in fibroblast-like synoviocytes via STAT3 and NF-kappaB signal pathways. Immunol Lett 127(2):100–107. https://doi.org/10.1016/j.imlet.2009.10.012

    Article  CAS  PubMed  Google Scholar 

  77. Benham H, Norris P, Goodall J, Wechalekar MD, FitzGerald O, Szentpetery A, Smith M, Thomas R, Gaston H (2013) Th17 and Th22 cells in psoriatic arthritis and psoriasis. Arthritis Res Ther 15(5):R136. https://doi.org/10.1186/ar4317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Mitra A, Raychaudhuri SK, Raychaudhuri SP (2012) Functional role of IL-22 in psoriatic arthritis. Arthritis Res Ther 14(2):R65. https://doi.org/10.1186/ar3781

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Ouyang W (2010) Distinct roles of IL-22 in human psoriasis and inflammatory bowel disease. Cytokine Growth Factor Rev 21(6):435–441. https://doi.org/10.1016/j.cytogfr.2010.10.007

    Article  CAS  PubMed  Google Scholar 

  80. Zenewicz LA, Yancopoulos GD, Valenzuela DM, Murphy AJ, Stevens S, Flavell RA (2008) Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity 29(6):947–957. https://doi.org/10.1016/j.immuni.2008.11.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Edwards JC (1994) The nature and origins of synovium: experimental approaches to the study of synoviocyte differentiation. J Anat 184(Pt 3):493–501

    PubMed  PubMed Central  Google Scholar 

  82. Choi SJ, Cruz JC, Craig F, Chung H, Devlin RD, Roodman GD, Alsina M (2000) Macrophage inflammatory protein 1-alpha is a potential osteoclast stimulatory factor in multiple myeloma. Blood 96(2):671–675

    Article  CAS  PubMed  Google Scholar 

  83. Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H (2006) Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 54(8):2665–2673. https://doi.org/10.1002/art.21972

    Article  PubMed  Google Scholar 

  84. Apostolakos J, Durant TJ, Dwyer CR, Russell RP, Weinreb JH, Alaee F, Beitzel K, McCarthy MB, Cote MP, Mazzocca AD (2014) The enthesis: a review of the tendon-to-bone insertion. Muscles Ligaments Tendons J 4(3):333–342

    Article  PubMed  PubMed Central  Google Scholar 

  85. McGonagle D, Lories RJ, Tan AL, Benjamin M (2007) The concept of a "synovio-entheseal complex" and its implications for understanding joint inflammation and damage in psoriatic arthritis and beyond. Arthritis Rheum 56(8):2482–2491. https://doi.org/10.1002/art.22758

    Article  PubMed  Google Scholar 

  86. Araujo EG, Schett G (2020) Enthesitis in psoriatic arthritis (Part 1): pathophysiology. Rheumatology (Oxford) 59(Supplement_1):i10–i14. https://doi.org/10.1093/rheumatology/keaa039

    Article  CAS  Google Scholar 

  87. Paulissen SM, van Hamburg JP, Davelaar N, Asmawidjaja PS, Hazes JM, Lubberts E (2013) Synovial fibroblasts directly induce Th17 pathogenicity via the cyclooxygenase/prostaglandin E2 pathway, independent of IL-23. J Immunol 191(3):1364–1372. https://doi.org/10.4049/jimmunol.1300274

    Article  CAS  PubMed  Google Scholar 

  88. Gruneboom A, Hawwari I, Weidner D, Culemann S, Muller S, Henneberg S, Brenzel A, Merz S, Bornemann L, Zec K, Wuelling M, Kling L, Hasenberg M, Voortmann S, Lang S, Baum W, Ohs A, Kraff O, Quick HH, Jager M, Landgraeber S, Dudda M, Danuser R, Stein JV, Rohde M, Gelse K, Garbe AI, Adamczyk A, Westendorf AM, Hoffmann D, Christiansen S, Engel DR, Vortkamp A, Kronke G, Herrmann M, Kamradt T, Schett G, Hasenberg A, Gunzer M (2019) A network of trans-cortical capillaries as mainstay for blood circulation in long bones. Nat Metab 1(2):236–250. https://doi.org/10.1038/s42255-018-0016-5

    Article  PubMed  PubMed Central  Google Scholar 

  89. Cambre I, Gaublomme D, Burssens A, Jacques P, Schryvers N, De Muynck A, Meuris L, Lambrecht S, Carter S, de Bleser P, Saeys Y, Van Hoorebeke L, Kollias G, Mack M, Simoens P, Lories R, Callewaert N, Schett G, Elewaut D (2018) Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis. Nat Commun 9 (1):4613. https://doi.org/10.1038/s41467-018-06933-4

  90. Sherlock JP, Joyce-Shaikh B, Turner SP, Chao CC, Sathe M, Grein J, Gorman DM, Bowman EP, McClanahan TK, Yearley JH, Eberl G, Buckley CD, Kastelein RA, Pierce RH, Laface DM, Cua DJ (2012) IL-23 induces spondyloarthropathy by acting on ROR-gammat+ CD3+CD4-CD8- entheseal resident T cells. Nat Med 18(7):1069–1076. https://doi.org/10.1038/nm.2817

    Article  CAS  PubMed  Google Scholar 

  91. Schett G, Lories RJ, D'Agostino MA, Elewaut D, Kirkham B, Soriano ER, McGonagle D (2017) Enthesitis: from pathophysiology to treatment. Nat Rev Rheumatol 13(12):731–741. https://doi.org/10.1038/nrrheum.2017.188

    Article  CAS  PubMed  Google Scholar 

  92. Soare A, Weber S, Maul L, Rauber S, Gheorghiu AM, Luber M, Houssni I, Kleyer A, von Pickardt G, Gado M, Simon D, Rech J, Schett G, Distler JHW, Ramming A (2018) Cutting edge: homeostasis of innate lymphoid cells is imbalanced in psoriatic arthritis. J Immunol 200 (4):1249-1254. https://doi.org/10.4049/jimmunol.1700596

  93. McGonagle D, Wakefield RJ, Tan AL, D'Agostino MA, Toumi H, Hayashi K, Emery P, Benjamin M (2008) Distinct topography of erosion and new bone formation in achilles tendon enthesitis: implications for understanding the link between inflammation and bone formation in spondylarthritis. Arthritis Rheum 58(9):2694–2699. https://doi.org/10.1002/art.23755

    Article  PubMed  Google Scholar 

  94. Yago T, Nanke Y, Ichikawa N, Kobashigawa T, Mogi M, Kamatani N, Kotake S (2009) IL-17 induces osteoclastogenesis from human monocytes alone in the absence of osteoblasts, which is potently inhibited by anti-TNF-alpha antibody: a novel mechanism of osteoclastogenesis by IL-17. J Cell Biochem 108(4):947–955. https://doi.org/10.1002/jcb.22326

    Article  CAS  PubMed  Google Scholar 

  95. Yarilina A, Xu K, Chen J, Ivashkiv LB (2011) TNF activates calcium-nuclear factor of activated T cells (NFAT)c1 signaling pathways in human macrophages. Proc Natl Acad Sci U S A 108(4):1573–1578. https://doi.org/10.1073/pnas.1010030108

    Article  PubMed  PubMed Central  Google Scholar 

  96. Sato K, Suematsu A, Okamoto K, Yamaguchi A, Morishita Y, Kadono Y, Tanaka S, Kodama T, Akira S, Iwakura Y, Cua DJ, Takayanagi H (2006) Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med 203(12):2673–2682. https://doi.org/10.1084/jem.20061775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. El-Zayadi AA, Jones EA, Churchman SM, Baboolal TG, Cuthbert RJ, El-Jawhari JJ, Badawy AM, Alase AA, El-Sherbiny YM, McGonagle D (2017) Interleukin-22 drives the proliferation, migration and osteogenic differentiation of mesenchymal stem cells: a novel cytokine that could contribute to new bone formation in spondyloarthropathies. Rheumatology (Oxford) 56(3):488–493. https://doi.org/10.1093/rheumatology/kew384

    Article  CAS  Google Scholar 

  98. Liao C, Zhang C, Jin L, Yang Y (2020) IL-17 alters the mesenchymal stem cell niche towards osteogenesis in cooperation with osteocytes. Journal of Cellular Physiology 235(5):4466–4480. https://doi.org/10.1002/jcp.29323

    Article  CAS  PubMed  Google Scholar 

  99. Shaw AT, Maeda Y, Gravallese EM (2016) IL-17A deficiency promotes periosteal bone formation in a model of inflammatory arthritis. Arthritis Res Ther 18(1):104. https://doi.org/10.1186/s13075-016-0998-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. van Tok MN, van Duivenvoorde LM, Kramer I, Ingold P, Pfister S, Roth L, Blijdorp IC, van de Sande MGH, Taurog JD, Kolbinger F, Baeten DL (2019) Interleukin-17A inhibition diminishes inflammation and new bone formation in experimental spondyloarthritis. Arthritis Rheumatol 71(4):612–625. https://doi.org/10.1002/art.40770

    Article  CAS  PubMed  Google Scholar 

  101. Li X, Wang J, Zhan Z, Li S, Zheng Z, Wang T, Zhang K, Pan H, Li Z, Zhang N, Liu H (2018) Inflammation intensity-dependent expression of osteoinductive Wnt proteins is critical for ectopic new bone formation in ankylosing spondylitis. Arthritis Rheumatol 70(7):1056–1070. https://doi.org/10.1002/art.40468

    Article  CAS  PubMed  Google Scholar 

  102. Ikebuchi Y, Aoki S, Honma M, Hayashi M, Sugamori Y, Khan M, Kariya Y, Kato G, Tabata Y, Penninger JM, Udagawa N, Aoki K, Suzuki H (2018) Coupling of bone resorption and formation by RANKL reverse signalling. Nature 561(7722):195–200. https://doi.org/10.1038/s41586-018-0482-7

    Article  CAS  PubMed  Google Scholar 

  103. Jacome-Galarza CE, Percin GI, Muller JT, Mass E, Lazarov T, Eitler J, Rauner M, Yadav VK, Crozet L, Bohm M, Loyher PL, Karsenty G, Waskow C, Geissmann F (2019) Developmental origin, functional maintenance and genetic rescue of osteoclasts. Nature 568(7753):541–545. https://doi.org/10.1038/s41586-019-1105-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Hasegawa T, Kikuta J, Sudo T, Matsuura Y, Matsui T, Simmons S, Ebina K, Hirao M, Okuzaki D, Yoshida Y, Hirao A, Kalinichenko VV, Yamaoka K, Takeuchi T, Ishii M (2019) Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1. Nat Immunol 20(12):1631–1643. https://doi.org/10.1038/s41590-019-0526-7

    Article  CAS  PubMed  Google Scholar 

  105. Klingberg E, Bilberg A, Bjorkman S, Hedberg M, Jacobsson L, Forsblad-d'Elia H, Carlsten H, Eliasson B, Larsson I (2019) Weight loss improves disease activity in patients with psoriatic arthritis and obesity: an interventional study. Arthritis Res Ther 21(1):17. https://doi.org/10.1186/s13075-019-1810-5

    Article  PubMed  PubMed Central  Google Scholar 

  106. Klingberg E, Bjorkman S, Eliasson B, Larsson I, Bilberg A (2020) Weight loss is associated with sustained improvement of disease activity and cardiovascular risk factors in patients with psoriatic arthritis and obesity: a prospective intervention study with two years of follow-up. Arthritis Res Ther 22(1):254. https://doi.org/10.1186/s13075-020-02350-5

    Article  PubMed  PubMed Central  Google Scholar 

  107. Love TJ, Zhu Y, Zhang Y, Wall-Burns L, Ogdie A, Gelfand JM, Choi HK (2012) Obesity and the risk of psoriatic arthritis: a population-based study. Ann Rheum Dis 71(8):1273–1277. https://doi.org/10.1136/annrheumdis-2012-201299

    Article  PubMed  Google Scholar 

  108. Hotamisligil GS (2017) Inflammation, metaflammation and immunometabolic disorders. Nature 542(7640):177–185. https://doi.org/10.1038/nature21363

    Article  CAS  PubMed  Google Scholar 

  109. Jordan S, Tung N, Casanova-Acebes M, Chang C, Cantoni C, Zhang D, Wirtz TH, Naik S, Rose SA, Brocker CN, Gainullina A, Hornburg D, Horng S, Maier BB, Cravedi P, LeRoith D, Gonzalez FJ, Meissner F, Ochando J, Rahman A, Chipuk JE, Artyomov MN, Frenette PS, Piccio L, Berres ML, Gallagher EJ, Merad M (2019) Dietary intake regulates the circulating inflammatory monocyte pool. Cell 178(5):1102–1114 e1117. https://doi.org/10.1016/j.cell.2019.07.050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Lee AH, Dixit VD (2020) Dietary regulation of immunity. Immunity 53(3):510–523. https://doi.org/10.1016/j.immuni.2020.08.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Leavy O (2013) T cells: salt promotes pathogenic TH17 cells. Nat Rev Immunol 13(4):225. https://doi.org/10.1038/nri3432

    Article  CAS  PubMed  Google Scholar 

  112. Wilck N, Matus MG, Kearney SM, Olesen SW, Forslund K, Bartolomaeus H, Haase S, Mahler A, Balogh A, Marko L, Vvedenskaya O, Kleiner FH, Tsvetkov D, Klug L, Costea PI, Sunagawa S, Maier L, Rakova N, Schatz V, Neubert P, Fratzer C, Krannich A, Gollasch M, Grohme DA, Corte-Real BF, Gerlach RG, Basic M, Typas A, Wu C, Titze JM, Jantsch J, Boschmann M, Dechend R, Kleinewietfeld M, Kempa S, Bork P, Linker RA, Alm EJ, Muller DN (2017) Salt-responsive gut commensal modulates TH17 axis and disease. Nature 551(7682):585–589. https://doi.org/10.1038/nature24628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christopher Ritchlin.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Disclosures

Consultant for Amgen, Abbvie, Novartis, Pfizer, Janssen, UCB, Lilly, and BMS.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is a contribution to the Special issue on: Spondyloarthritis - Guest Editors: Robert Inman & Nigil Haroon

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ritchlin, C. Navigating the diverse immune landscapes of psoriatic arthritis. Semin Immunopathol 43, 279–290 (2021). https://doi.org/10.1007/s00281-021-00848-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00281-021-00848-x

Keywords

Navigation