MHC class II alleles associated with Th1 rather than Th17 type immunity drive the onset of early arthritis in a rat model of rheumatoid arthritis

Tuncel, Jonatan; Haag, Sabrina; Holmdahl, Rikard

doi:10.1002/eji.201646760

Cited by 19 publications

(11 citation statements)

References 67 publications

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“…Pristane is a natural saturated terpenoid alkane, and known to induce autoimmune diseases in rodents for researching the pathogenesis of rheumatoid arthritis and lupus [ 7 , 8 ]. PIA is a T-cell-driven arthritis model, which is not dependent on the administration of exogenous antigens [ 9 , 10 ].Thus, PIA is very suitable for studying the role of cytokines in the pathogenesis of RA.…”

Section: Introductionmentioning

confidence: 99%

Increased expression of Th17 cytokines and interleukin-22 correlates with disease activity in pristane-induced arthritis in rats

et al. 2017

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The objective of this study was to identify the key changed subtype of T helper cells (Th cells) and their cytokines in pristane-induced arthritis (PIA) in rats. The severity of arthritis was evaluated by body weight, clinical score, the perimeter of ankle and mid-paw and histological assessment of ankle joints. Cytokines of Th1, Th2 and Th17 were determined in the spleen and inguinal lymph nodes at 28 days after pristane injection by real-time qPCR. The mRNA levels of IL-22 receptors, IL-22R1 and IL-22BP, in the spleen were quantified by real-time qPCR. Additionally, IL-22 expression in synovial membrane was detected by Western blotting, and serum IL-22 concentration was determined by ELISA. Correlation between IL-22 concentration and clinical score was analyzed. By screening the cytokines of Th1, Th2 and Th17 expression profile, we found that the mRNA levels of Th17 cytokines were significantly increased in PIA rats. Particularly, a significant increase in the protein expression of IL-22 was determined in synovial membrane and serum from PIA rats, and correlated with clinical score. We conclude that IL-22 expression level was increased and correlated with disease severity, which indicated that IL-22 may play an important role in development of PIA, and was helpful to explorer the pathogenesis of rheumatoid arthritis.

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Section: Introductionmentioning

confidence: 99%

Increased expression of Th17 cytokines and interleukin-22 correlates with disease activity in pristane-induced arthritis in rats

et al. 2017

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“…Quantitative PCR analyses revealed that CD4 + T cells from the spleen of pristane-injected rats expressed lower levels of Th17associated cytokines than CD4 + T cells from dLNs, suggesting a difference in the proportion of Th17 cells (or in the relative expression of Il17 and Il22 transcripts) between the two organs. Therefore, given the importance of IL-17 in PIA [24], it is possible that spleen-, in contrast to LN-, derived T cells lack the properties necessary to sustain a chronic immune response. Moreover, as shown by Catron et al, tissue-draining LNs continue to be seeded by antigen-specific late-arriving T cells, which are enriched in central-memory cells, in the first several weeks after the primary immune response is over [40].…”

Section: Discussionmentioning

confidence: 99%

“…Anti-mouse IL-17A antibody (clone 17F3; mouse IgG1) and isotype control antibody (clone MOPC-21) were obtained from Bio X Cell (West Lebanon, NH, USA). Crossreactivity to rat IL-17 has been evaluated previously [24].…”

Section: Antibodies and Immunosuppressive Reagentsmentioning

confidence: 99%

“…Based on our previously published data showing that IFNγ-producing Th1 cells are critical for the early inflammatory response in PIA while IL-17 are more important for the perpetuation of disease [24], we set out to explore the expression of various cytokines and transcription factors in CD4 + T cells from LN and spleen. On day 13 after pristane injection, mRNA expression of Il17 and the Th17-associated cytokine, Il22, was approximately 60-80fold higher in CD4 + T cells from inguinal than mesenteric LNs (Fig.…”

Section: Cd4 + T Cells In Draining Lns Express High Levels Of Cytokinmentioning

confidence: 99%

“…Rats injected with pristane develop polyarticular arthritis with elevated levels of acute-phase reactants [17,18] and IgG rheumatoid factors [19]. Since the inoculum in PIA is free from exogenous antigens, T cells are believed to recognize self-antigens in the context of MHCII [20,21], and while self-antigens have been identified in PIA, e.g., collagen type XI [22] and hnRNP-A1 [23], the arthritogenic response appears to be polyclonal rather than directed towards a few major antigens [21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

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Self-reactive T cells induce and perpetuate chronic relapsing arthritis

et al. 2020

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Background: CD4 + T cells play a central role during the early stages of rheumatoid arthritis (RA), but to which extent they are required for the perpetuation of the disease is still not fully understood. The aim of the current study was to obtain conclusive evidence that T cells drive chronic relapsing arthritis. Methods: We used the rat pristane-induced arthritis model, which accurately portrays the chronic relapsingremitting disease course of RA, to examine the contribution of T cells to chronic arthritis. Results: Rats subjected to whole-body irradiation and injected with CD4 + T cells from lymph nodes of pristaneinjected donors developed chronic arthritis that lasted for more than 4 months, whereas T cells from the spleen only induced acute disease. Thymectomy in combination with irradiation enhanced the severity of arthritis, suggesting that sustained lymphopenia promotes T cell-driven chronic inflammation in this model. The ability of T cells to induce chronic arthritis correlated with their expression of Th17-associated transcripts, and while depletion of T cells in rats with chronic PIA led to transient, albeit significant, reduction in disease, neutralization of IL-17 resulted in almost complete and sustained remission. Conclusion: These findings show that, once activated, self-reactive T cells can sustain inflammatory responses for extended periods of time and suggest that such responses are promoted in the presence of IL-17.

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Stromal cells from perinatal and adult sources modulate the inflammatory immune response in vitro by decreasing Th1 cell proliferation and cytokine secretion

Khoury

Atala

Murphy

2019

Stem Cells Translational Medicine

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Many immune-mediated conditions are associated with a dysregulated imbalance toward a Th1 response leading to disease onset, severity, and damage. Many of the therapies such as immunomodulators or anti-TNF-α antibodies often fall short in preventing disease progression and ameliorating disease conditions. Thus, new therapies that can target inflammatory environments would have a major impact in preventing the progression of inflammatory diseases. We investigated the role of human stromal cells derived from the amniotic fluid (AFSCs), the placenta (PLSCs), and bone marrow-derived mesenchymal stromal cells (BM-MSCs) in modulating the inflammatory response of in vitro-stimulated circulating blood-derived immune cells. Immune cells were isolated from the blood of healthy individuals and stimulated in vitro with antigens to activate inflammatory responses to stimuli. AFSC, BM-MSCs, and PLSCs were cocultured with stimulated leukocytes, neutrophils, or lymphocytes. Inflammatory cytokine production, neutrophil migration, enzymatic degranulation, T cell proliferation, and subsets were evaluated. Coculture of all three stromal cell types decreased the gene expression of inflammatory cytokines and enzymes such as IL-1β, IFN-γ, TNF-α, neutrophil elastase, and the transcription factor NF-κB in lipopolysaccharide-stimulated leukocytes.With isolated phytohemagglutinin-stimulated peripheral blood mononuclear cells, cells coculture leads to a decrease in lymphocyte proliferation. This effect correlated with decreased numbers of Th1 lymphocytes and decreased secreted levels of IFN-γ.

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MHC class II alleles associated with Th1 rather than Th17 type immunity drive the onset of early arthritis in a rat model of rheumatoid arthritis

Cited by 19 publications

References 67 publications

Increased expression of Th17 cytokines and interleukin-22 correlates with disease activity in pristane-induced arthritis in rats

Increased expression of Th17 cytokines and interleukin-22 correlates with disease activity in pristane-induced arthritis in rats

Self-reactive T cells induce and perpetuate chronic relapsing arthritis

Stromal cells from perinatal and adult sources modulate the inflammatory immune response in vitro by decreasing Th1 cell proliferation and cytokine secretion

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