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Immunobiology of T Cells in Sjögren’s Syndrome

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Abstract

Sjögren’s syndrome (SjS) is a systemic autoimmune disease marked by xerostomia (dry mouth), keratoconjunctivitis sicca (eye dryness), and other systematic disorders. Its pathogenesis involves an inflammatory process that is characterized by lymphocytic infiltration into exocrine glands and other tissues. Although the development of ectopic lymphoid tissue and overproduction of autoantibodies by hyperactive B cells suggest that they may promote SjS development, treatment directed towards them fails to induce significant laboratory or clinical improvement. T cells are overwhelming infiltrators in most phases of the disease, and the involvement of multiple T cell subsets of suggests the extraordinary complexity of SjS pathogenesis. The factors, including various cellular subtypes and molecules, regulate the activation and suppression of T cells. T cell activation induces inflammatory cell infiltration, B cell activation, tissue damage, and metabolic changes in SjS. Knowledge of the pathways that link these T cell subtypes and regulation of their activities are not completely understood. This review comprehensively summarizes the research progress and our understanding of T cells in SjS, including CD4+ T cells, CD8+ TRM cells, and innate T cells, to provide insights into for clinical treatment.

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Abbreviations

APCs:

Antigen-presenting cells

AQP:

Aquaporin

BAFF:

B cell activating factor

Cat S:

Cathepsin S

cTfh:

Circulating follicular helper T cell

cTfr:

Circulating follicular regulatory T cell

CCL:

Chemokine (C-C motif) ligand

CXCL:

Chemokine (C-X-C motif) ligand

CCR:

CXC chemokine receptor

CXCR:

CXC chemokine receptor

DCs:

Dendritic cells

DN T cells:

CD4&CD8 double-negative T cells

EGMs:

Extraglandular manifestations

ELS:

Ectopic lymphoid-like structures

GC:

Germinal center

GLS:

GC-like structures

GWAS:

Genome-wide association studies

LAMP:

Lysosome-associated membrane glycoprotein

ICAM:

Intercellular adhesion molecule

ICOS:

Inducible T cell co-stimulator

ICOSL:

ICOS ligand

IFN:

Interferon

IFN-γR:

IFN-γ receptor

IL:

Interleukin

IL-22R:

IL-22 receptor

iNKT cell:

Invariant natural killer T cell

MAIT cell:

Mucosal-associated invariant T cell

MDC:

Macrophage-derived chemokine

MetS:

Metabolic syndrome

MHC:

Major histocompatibility complex class

MMP:

Matrix metalloproteinase

NK:

Natural killer

NOD:

Non-obese diabetic mouse

pDCs:

Plasmacytoid DC cells

ROR:

RAR-related orphan receptor

SGEC:

Salivary gland epithelial cell

SjS:

Sjögren’s syndrome

SLE:

Systemic lupus erythematosus

SLO:

Secondary lymphoid organs

S1P:

Sphingosine 1-phosphate

TARC:

Thymus and activation-regulated chemokine

Tfh:

Follicular helper T cell

Tfr:

Follicular regulatory T cell

TGF-β:

Transforming growth factor beta

Th:

Helper T cell

TLRs:

Toll-like receptors

TNF-α:

Tumor necrosis factor alpha

Treg:

Regulatory T cell

TRM:

Tissue resident memory T cell

Tr1:

Type 1 regulatory T cell

VCAM-1:

Vascular cell adhesion molecule-1.

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Authorship

Yuan Yao, Jin-Fen Ma, Ting Xu, and Cai-Yue Gao wrote the manuscript. Yuan Yao, JIn-Fen Ma, and Cai-Yue Gao designed and drew the figures; Christopher Chang, Patrick M. Eric Gershwin, and Zhe-Xiong Lian wrote and edited the manuscript.

Funding

This work is supported by the Program for Guangdong Introducing Innovative and Entrepreneurial Teams (2017ZT07S054), the National Key R&D Program of China (2017YFA0205600), and the National Natural Science Foundation of China (81901653, 81701597).

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  1. Yuan Yao and Jin-Fen Ma contributed equally to this work.

Authors and Affiliations

  1. Digestive Disease Institute, Guangzhou First People’s Hospital and Institutes for Life Sciences, South China University of Technology, Guangzhou, 510006, China

    Yuan Yao, Jin-Fen Ma, Cai-Yue Gao & Zhe-Xiong Lian

  2. Chronic Disease Laboratory, Institutes for Life Sciences and School of Medicine, South China University of Technology, Guangzhou, 510006, Guangdong, China

    Yuan Yao, Jin-Fen Ma, Cai-Yue Gao & Zhe-Xiong Lian

  3. Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA, USA

    Christopher Chang & M. Eric Gershwin

  4. Joe DiMaggio Children’s Hospital, Hollywood, FL, USA

    Christopher Chang

  5. Department of Rheumatology and Clinical Immunology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, No. 106, Zhongshan 2nd Road, Guangzhou, 510080, China

    Ting Xu

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Yao, Y., Ma, JF., Chang, C. et al. Immunobiology of T Cells in Sjögren’s Syndrome. Clinic Rev Allerg Immunol 60, 111–131 (2021). https://doi.org/10.1007/s12016-020-08793-7

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  • DOI: https://doi.org/10.1007/s12016-020-08793-7

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