Human lung transplant recipients undergoing rejection induce circulatory exosomes with lung self-antigens (SAgs), K-alpha 1 Tubulin and Collagen V, and immunization of C57BL/6 mice with exosomes induced obliterative airway disease (HEI-OAD). We analyzed whether exosomes with SAgs induced immunity in microRNA-155 knockout mice (miR-155KO), as microRNA-155 is an immune regulator. C57BL/6 and miR-155KO

T cell responses to antigen are initiated by engagement of the T cell receptor (TCR)1, leading to activation of diverse signaling cascades, including an incompletely defined pathway that triggers rapid remodeling of the actin cytoskeleton. Defects in control of actin dynamics and organization are associated with several human immunodeficiency diseases, emphasizing the importance of cytoskeletal remodeling

FOXP3+ regulatory T cells (Tregs) constitute a critical barrier that enforces tolerance to both the self-peptidome and the extended-self peptidome to ensure tissue-specific resistance to autoimmune, allergic, and other inflammatory disorders. Here, we review intuitive models regarding how T cell antigen receptor (TCR) specificity and antigen recognition efficiency shape the Treg and conventional T

Structure-activity relationships provide insight into the binding interactions of beta-glycosphingolipids (GSLs) with both the TCR and the CD1d molecules, as well as the subsequent immunologic response of regulatory NKT cells. Aim To determine the effects of synthetic GSL structures on their immune modulatory functions. Methods GSLs of various structures were tested in vitro and in an animal model

Tregs are the immune system’s in-house combatants against pathological immune activation. Because they are vital to maintenance of peripheral tolerance, it is important to understand how they perform their functions. To this end, various mechanisms have been proposed for Treg-mediated immune inhibition. A major group of mechanisms picture Tregs as skilled thieves stealing a plethora of molecules that

Immune responses to non-pathogenic yeasts induced within the draining lymph node remain to be understood. In this study, we have investigated the changes in lymphocytes and their activity in skin-draining lymph nodes in response to transdermally injected zymosan (component of the yeast cell wall). Zymosan elicited the transient increase of B cell number and activation status without affecting the capacity

The CBM complex, which is composed of the proteins CARMA1, BCL10, and MALT1, serves multiple pivotal roles as a mediator of T-cell receptor and B-cell receptor-dependent NF-κB induction and lymphocyte activation. CARMA1, BCL10, and MALT1 are each proto-oncoproteins and dysregulation of CBM signaling, as a result of somatic gain-of-function mutation or chromosomal translocation, is a hallmark of multiple

Toll-like receptor (TLR)4 and TLR9 agonists, MPL and CpG, are used as adjuvants in vaccines and have been investigated for their combined potential. However, how these two combined agonists regulate transcriptional changes in innate immune cells and cells at the site of vaccination has not been thoroughly investigated. Here, we utilized transcriptomics to investigate how CpG, MPL, and CpG + MPL impact

The IL-7 receptor alpha chain (IL-7Rα or CD127) can be differentially expressed in memory CD8+ T cells. Here we investigated whether IL-7Rα could serve as a key molecule in defining a comprehensive landscape of heterogeneity in human effector memory (EM) CD8+ T cells using high-dimensional Cytometry by Time-Of-Flight (CyTOF) and single-cell RNA-seq (scRNA-seq). IL-7Rα had diverse, but organized, expressional

B cells with regulatory properties (Bregs) were identified in human and in mice among different B-cell subsets. Their regulatory properties rely mainly on the production of anti-inflammatory cytokines, in particular IL10, IL-35 and TGFβ, and were extensively studied in mouse models of autoimmune and inflammatory diseases. However, the exact nature of the stimulatory signals conferring regulatory properties

Mycobacterium tuberculosis (Mtb) is an intracellular pathogen known to persist in host cells. The apoptotic response of macrophages serves as a defense mechanism to inhibit the growth of intracellular bacteria, the failure of which can favor the spread of the pathogen to new cells. However, the mycobacterial components that regulate cell death and the related underlying mechanisms remain poorly understood

Macrophages are key players in wound healing- along with mediating the acute inflammatory response, macrophages activate cutaneous epithelial cells and promote tissue repair. Diabetes complications are accompanied with persistent inflammation and macrophage malfunction, including diabetic chronic wounds. Several studies indicate that hyperglycemia induces various alterations that affect macrophage

CARD14 is a scaffold molecule predominantly expressed in keratinocytes and genetic variants in the CARD14 gene confer an increased risk of inflammatory skin disease. Due to its association with common skin diseases psoriasis and atopic dermatitis, the biological function of CARD14 is of relevant interest to human health. CARD14 recruits BCL10 and MALT1 to form the CARD-BCL10-MALT1 complex, which modulates

Transient vestibular organ deafferentation, such that is caused by traumatic tissue injury, is presently addressed by corticosteroid therapy. However, restoration of neurophysiological properties is rarely achieved. Here, it was hypothesized that the tissue-protective attributes of α1-antityrpsin (AAT) may promote restoration of neuronal function. Inner ear injury was inflicted by unilateral labyrinthectomy

The lipopolysaccharide (LPS) of gram-negative bacteria is recognized on human monocytes and macrophages by TLR4 and MD2 and induces production of inflammatory cytokines; the co-stimulation with LPS plus aggregated IgG increases the cytokine production, mediated by CD32a, an Fc-γ receptor. We stimulated the human monocytic cell line THP-1 with LPS from E. coli or LPS + soluble human IgG (sIgG) and TNF-α

Peptidoglycan recognition protein 3 (PGlyRP3) is a pattern recognition protein found in the gut epithelia and proven to have an anti-inflammatory effect in response to dietary lipids via the upregulation of PPARγ. We have reported an in vitro anti-inflammatory action for prebiotic oligosaccharides in the intestinal caco2 cells through stimulation of PPARγ and PGlyRP3. In the present study, this effect

Statin drugs are widely employed in the clinic to reduce serum cholesterol. Due to their HMG CoA reductase (HMGCR) antagonism, statins also reduce isoprenyl lipids necessary for the membrane anchorage and signaling of small G-proteins in the Ras superfamily. We previously found that statins suppress IgE-mediated mast cell activation, suggesting these drugs might be useful in treating allergic disease

Non-HLA antibody responses following solid organ transplantation have become increasingly emphasised, with several large clinical series suggesting that such responses contribute to late graft failure. Many of the responses described recognise both recipient and donor moieties of the target antigen and thus represent auto-, rather than allo-immunity. Within this rapidly evolving field, many questions

The natural bioactive glycerophospholipid lysophosphatidic acid (LPA) binds to its cognate G protein-coupled receptors (GPCRs) on the cell surface to promote the activation of several transcription factors, including NF-κB. LPA-mediated activation of NF-κB relies on the formation of a signalosome that contains the scaffold CARMA3, the adaptor BCL10 and the paracaspase MALT1 (CBM complex). The CBM complex

Protective immune response to chlamydial infection is largely dependent on cell-mediated immune responses with IFN-γ production. Recent studies have shown the critical role of NK cells in bridging innate and adaptive immune responses. In this study, we investigated the effect of NK cells on T cell responses during Chlamydophila pneumoniae (Cpn) lung infection. The results showed that NK cells play

BENTA (B cell Expansion with NF-κB and T cell Anergy) is a novel lymphoproliferative disorder caused by germline, gain-of-function (GOF) mutations in the lymphocyte-restricted scaffolding protein CARD11. Similar somatic CARD11 mutations are found in lymphoid malignancies such as diffuse large B cell lymphoma (DLBCL). Normally, antigen receptor (AgR) engagement converts CARD11 into an active conformation

Previously our lab has shown that co-stimulation of human T cells through different co-stimulatory molecules tune differentiation to different phenotypes. An open question is where in the signaling pathways induced by the co-stimulation do differences occur that contribute to outcome of differentiation. In this project, we investigate the early signaling process by comparing events that follow engagement

The in vivo proliferation and viability of transfused engineered T cells markedly limits the long-term effect of adoptive cell therapy on tumors. The therapeutic efficacy and proliferative potential of T cells are reported to be dependent on the differentiation status of T cells. The T cells at the early stage of progressive differentiation have a long lifespan, strong proliferative potential, and

Given the promising results in human lupus with B cell depletion, we tested whether in vivo cytotoxic T lymphocyte (CTL) could eliminate autoreactive B cells in the setting of murine lupus. Using the parent-into-F1 (P → F1) model to generate CTL that eliminate B cells, we found that transfer ofNZB parental splenocytes into lupus-prone female NZB/W F1 mice resulted in profound B cell reduction whereas

Tumor associated macrophages (TAMs) are the most frequent immune cells within tumor microenvironment (TME). There is growing evidence that TAMs are involved in tumor progression via multiple mechanisms. TAMs create an immunosuppressive TME by producing growth factors, chemokines, and cytokines which modulate recruitment of immune cells and inhibit anti-tumor responses. They also serve as angiogenesis

Thymic stromal lymphopoietin (TSLP) acts on dendritic cells (DCs), which prime helper T (Th) cells to become type 2 cytokine producing cells. Recently, a different set of populations of TSLP-responsive DCs has been discovered. Here, we identified two populations of CD103loEpCAMhi migratory DCs (fraction I and fraction II) that accumulated in skin-draining lymph nodes in response to TSLP expressed in

The CARMA1-BCL10-MALT1 (CBM) complex couples antigen receptors to the activation of Nuclear Factor κB (NF-κB) transcription factors in T/B lymphocytes. Within this signalosome, the MALT1 paracaspase serves dual roles: it is a crucial adaptor for signal transduction to NF-κB signaling, and a protease that shapes NF-κB activity and lymphocyte activation. Although a subtle choreography of ubiquitination

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why

THC is the main psychoactive compound found in marijuana. A number of studies over the past few decades, both in vitro and in vivo, have demonstrated that THC down-regulates the inflammatory process through various mechanisms. Similar findings have been demonstrated with CBD, the other major bioactive component of marijuana. Given the essential role that inflammation plays in early wound healing, it

Human placenta-derived mesenchymal stromal cells (hPMSCs) are promising candidates for the treatment of graft-versus-host disease (GVHD), which is associated with high IL-1β levels. In this study, the effects of IL-1β and hPMSCs on each other were investigated by analyzing the proportion of Th1, Th2 and CD4+IL-10+ T cells and PD-L1 expression, as well as the adhesion, migration, and proliferation of

Glioblastoma is one of the deadliest cancers. Chimeric antigen receptor (CAR)-T cell therapy against solid tumors has been far from satisfactory largely due to the immunosuppressive tumor microenvironment, such as PD-1 mediated T cell exhaustion. In the present study, we investigated the combined antitumor effects of anti-EGFR variant III CAR-T cell therapy and PD-1 checkpoint blockade on glioblastoma

The checkpoint molecule human leukocyte antigen (HLA)-G has restricted tissue expression, and plays a role in the establishment of maternal tolerance to the semi-allogenic fetus during pregnancy by expression on the trophoblast cells in the placenta. HLA-G exists in at least seven well-described mRNA isoforms, of which four are membrane-bound and three soluble. Regulation of the tissue expression of

B-1a cells represent a distinct B cell population with unique phenotype, self-renewing capacity and restricted Igμ repertoire. They primarily locate in body cavity and also exist in spleen. The different subpopulations of B-1a cells are heavily affected by local environment. Our previous studies revealed that MARVEL-domain-containing membrane protein, CMTM7, was involved in B-1a cell development. Here

While T cells play a critical role in protective immunity against infection, they are also responsible for graft rejection in the setting of transplantation. T cell differentiation is regulated by both intrinsic transcriptional pathways as well as extrinsic factors such as antigen encounter and the cytokine milieu. Herein, we review recent discoveries in the transcriptional regulation of T cell differentiation

Asthma is an inflammatory disease of the airways and numerous cytokines contribute to this pathogenesis. It is shown that challenge of airways with IL-33 induces asthma-like pathological changes in mice, but the possible downstream cytokines in this process remain to be characterised. To explore this, we compared changes in the airways of wildtype (WT) and IL-9 deficient mice challenged with IL-33

Nonhuman primates (NHP) are important pre-clinical models for evaluation of the safety and efficacy of the most promising potential therapeutic advances in organ transplantation based on rodent studies. Although rare, dendritic cells (DC) play important roles in preservation of self tolerance and DC with immunoregulatory properties (regulatory DC; DCreg) can promote transplant tolerance in rodents

Optical imaging is a valuable tool to visualise biological processes in the context of the tissue. Each imaging modality provides the biologist with different types of information – cell dynamics and migration over time can be tracked with time-lapse imaging (e.g. intra-vital imaging); an overview of whole tissues can be acquired using optical clearing in conjunction with light sheet microscopy; finer

Pattern recognition receptors (PRRs) are germline-encoded sensors best characterized for their critical role in host defense. However, there is accumulating evidence that organ transplantation induces the release or display of molecular patterns of cellular injury and death that trigger PRR-mediated inflammatory responses. There are also new insights that indicate PRRs are able to distinguish between

Asthma is a disease of the respiratory system that is commonly considered a T-helper 2 (Th2) cell-associated inflammatory disease. Group 2 innate lymphoid cells (ILC2s) promote the inflammatory responses in asthma by secreting type 2 cytokines. Interleukin (IL)-9 also serves as a promoting factor in asthma and it is well known that ILC2s have an autocrine effect of IL-9 to sustain their survival and

AIMS To investigate whether placenta-derived mesenchymal stromal cells (hPMSCs) have immunoregulatory effects on PD-1+ T cell generation by controlling ROS production and thus alleviating GVHD. MAIN METHODS Flow cytometry was used to analyze the percentage of PD-1+ T cells, as well as the generation of ROS, GSH and GST in PD-1+ T cells. The expression of GST in the spleen and liver was analyzed by

Toll-like receptor (TLR) 2/1 signalling is linked to autophagy through transcriptional actions of the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-vitamin D receptor (VDR) complex. Population-specific effects have been reported for TLR2/1-VDR signalling. We hypothesized that population effects extend to autophagy and are influenced by vitamin D status. Serum 25(OH)D3 of healthy South Africans (Black individuals

Mice that express a single transgenic T cell receptor have a low incidence of T cell lymphoma development. We investigated whether this tumor development is restricted by surveillance mechanisms that are exerted by IL-15-dependent cells. Lymphoma incidence was increased to between 30 and 60% when TCR transgenes were expressed in IL-15-deficient mice. Mice in which NK cells had been depleted genetically

The gastrointestinal (GI) tract microbiota is an environmental factor that regulates host immunity in allo-transplantation (allo-Tx). It is required for the development of resistance against pathogens and the stabilization of mucosa-associated lymphoid tissue. The gut-microbiota axis may also precipitate allograft rejection by producing metabolites that activate host cell-mediated and humoral immunity

Mast cells (MCs) are engaged in host defense against various pathogens as they are equipped with pattern recognition receptors (PRRs). Among PRRs expressed on MCs, there are also molecules recognizing components of the fungal cell wall, which are able to induce cellular activation and response. However, little information is available concerning the MC activation by various fungal-derived components

B7-H3 as a newly identified costimulatory molecule that belongs to B7 ligand family, is broadly expressed in both lymphoid and non-lymphoid tissues. The overexpression of B7-H3 has been verified to be correlated with the poor prognosis and poor clinical outcome of several human cancers. In recent years, researchers reveal that B7-H3 is involved in the pathogenesis of various autoimmune diseases, such

We delineated the expression of DAP12 (DNAX-Activating Protein) and its associated receptors, TREM-1, TREM-2 and MDL-1 in pig alveolar monocyte/macrophages (AMM) that have attained M1 or M2 phenotypes. Pig AMM stimulated in vitro with IFN-γ and IL-4 induced the expression of M1 (TNFα and iNOS) and M2 (ARG1 and no MMR) phenotypic markers, respectively. In influenza virus infected pigs at seven days

Chimeric antigen receptors (CAR) utilize costimulatory domains to enhance anti-tumor efficacy. However, it is unclear which costimulatory domain is preferable. Therefore, the intracellular domains of CD28, Dap10, 41BB, GITR, ICOS, or OX40 were compared in a murine chimeric PD1 (chPD1) receptor that targets tumor-associated PD1 ligands. Upon antigen restimulation, T cells expressing chPD1-CD28 receptors

Human rhinovirus (hRV) is the most common cause of asthma exacerbation characterized by clinical and pathophysiological heterogeneity. Steroid-sensitive, Th2 type-eosinophilic asthma has been somewhat studied, but hRV-induced neutrophilic asthma exacerbation is poorly understood. Here, CCR5 was found to play a role in attenuating neutrophilic airway inflammation in hRV-induced asthma exacerbation using

Cellular metabolism is central to T cell function and proliferation, with most of the research to date focusing on cancer and autoimmunity. Cellular metabolism is associated with a host of physiological phenomena, from epigenetic changes, to cellular function and fate. For the purpose of this review, we will discuss the metabolism of T cells relating to their differentiation and function. We will cover

Many aspects remain elusive of the mechanisms governing T cell quiescence. Here we show that E protein activity helps to establish a quiescent program in naïve T cells. Decreased E protein activity, as the consequence of enforced expression of an Id1 transgene, led to the accumulation of CD4+CD44hi T cells. The naïve CD4+ T cells from this transgenic strain mounted a vigorous proliferative response