Synovial IL-9 facilitates neutrophil survival, function and differentiation of Th17 cells in rheumatoid arthritis

Chowdhury, Kaustav; Kumar, Uma; Das, Soumabha; Chaudhuri, Jaydeep; Kumar, Prabin; Kanjilal, Maumita; Ghosh, Parashar; Sircar, Geetabali; Basyal, Ravi Kiran; Kanga, Uma; Bandyopadhaya, Santu; Mitra, Dipendra Kumar

doi:10.1186/s13075-017-1505-8

Cited by 53 publications

(49 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In numerous experimental autoimmune disease models, Th9 cells have been found as primary contributors to the inflammatory progression (25). Previously, it had been indicated that Th9 cells are increased in RA patients compared to healthy controls (11,26,27). Our results confirmed the findings of earlier studies regarding the significant increase in the frequency of circulating Th9 cells in RA patients.…”

Section: Discussionsupporting

confidence: 91%

Frequency of Th9 Cells in Different Stages of Rheumatoid Arthritis

et al. 2019

View full text Add to dashboard Cite

Background and Objectives: T helper (Th) lymphocytes play a key role in the pathogenesis of autoimmune diseases. As a new subset of lymphocytes, Th9 is thought to be involved in a wide range of disorders including rheumatoid arthritis (RA). In this study, we evaluated frequency of Th9 and Th2 cells and its correlation with disease activity in patients with different stages of RA. Methods: The frequency of circulating interleukin 9-and/or interleukin 4producing CD3 + CD8-T cells was determined among 41 patients with established RA, 14 patients with very early RA (VERA) and 23 healthy controls by flow cytometry analysis. Then, correlation of cell frequencies with disease activity score 28 (DAS-28) was assessed. Serum levels of interleukin 6 and anti-citrullinated peptide antibodies were measured by enzymelinked immunosorbent assay. Results: Frequency of Th9 cells was significantly higher in RA patients compared to healthy controls (P=0.009). Moreover, mean percentage of circulating Th9 cells in patients with inactive VERA was significantly higher than that in those with active disease (P=0.046). In addition, mean percentage of Th9 cells had a negative correlation with the DAS-28 (r=-0.568, P<0.05). There was no significant correlation between the mean serum level of interleukin 6 and percentage of Th2 and Th9 cells (P>0.05). Conclusion: Our results suggest that Th9 cells may have a potential role in RA initiation. Thus, targeting Th9 cells could be a promising strategy for advanced RA therapies.

show abstract

Section: Discussionsupporting

confidence: 91%

Frequency of Th9 Cells in Different Stages of Rheumatoid Arthritis

et al. 2019

View full text Add to dashboard Cite

show abstract

“…39 A recent study also demonstrated that IL-9 might facilitate the survival of neutrophils in rheumatoid arthritis. 40 Therefore, in our model it is possible that anti-IL-9 effectively reduced egg granulomatous inflammation and decreased inflammatory cell infiltration around the trapped eggs through mechanisms similar to those mentioned above.…”

Section: Discussionmentioning

confidence: 72%

Interleukin‐9 blockage reduces early hepatic granuloma formation and fibrosis during Schistosoma japonicum infection in mice

Zhan¹,

Ma²,

Jiang³

et al. 2019

Immunology

View full text Add to dashboard Cite

Summary Hepatic fibrosis induced by schistosomes is regulated by a complex network of cytokines. T helper type 9 (Th9) cells are a new type of effector T helper cells, which mainly secrete the specific cytokine interleukin‐9 (IL‐9). Interleukin‐9 has been shown to contribute to liver fibrosis in patients with chronic hepatitis B and in a mouse model due to carbon tetrachloride. However, the role of IL‐9 in schistosomiasis fibrosis remains unknown. In this study, we investigated the roles of IL‐9 in schistosomiasis through in vivo and in vitro studies. The in vivo studies found that neutralization of IL‐9 reduced liver granulomatous inflammation and collagen deposition around parasite eggs. The in vitro studies found that the treatment of primary hepatic stellate cells with IL‐9 induced a significant increase of collagen and α‐smooth‐muscle actin. Moreover, we also described the dynamics and relevance of IL‐9 and IL‐4 in mice infected with Schistosoma japonicum. We found that IL‐9 might appear more quickly and at higher levels than IL‐4. Hence, our findings indicated that IL‐9 might play a role in regulating hepatic fibrosis in early‐stage schistosomiasis and become a promising approach for regulating hepatic fibrosis caused by S. japonicum.

show abstract

“…As in human RA, multiple immune and inflammatory events and pathways are involved, including autoreactive Th1 and Th17 T cells, autoantibodies, proinflammatory cytokines, and activated, tissue‐destructive synovial cells . Moreover, synovial enrichment of Th9 cells shows a positive correlation with disease activity in RA, and synovial IL‐9 prolongs the survival of neutrophils, increases their matrix metalloproteinase 9 production, and facilitates Th17 cell differentiation .…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Murine Collagen‐Induced Arthritis by Targeting CD6

Ruth

Rasmussen

et al. 2020

Arthritis & Rheumatology

View full text Add to dashboard Cite

Objective CD6 is an important regulator of T cell function that interacts with the ligands CD166 and CD318. To further clarify the significance of CD6 in rheumatoid arthritis (RA), we examined the effects of targeting CD6 in the mouse model of collagen‐induced arthritis (CIA), using CD6‐knockout (CD6‐KO) mice and CD6‐humanized mice that express human CD6 in lieu of mouse CD6 on their T cells. Methods We immunized wild‐type (WT) and CD6 gene–KO mice with a collagen emulsion to induce CIA. For treatment studies using CD6‐humanized mice, mice were immunized similarly and a mouse anti‐human CD6 IgG (UMCD6) or control IgG was injected on days 7, 14, and 21. Joint tissues were evaluated for tissue damage, leukocyte infiltration, and local inflammatory cytokine production. Collagen‐specific Th1, Th9, and Th17 responses and serum levels of collagen‐specific IgG subclasses were also evaluated in WT and CD6‐KO mice with CIA. Results The absence of CD6 reduced 1) collagen‐specific Th9 and Th17, but not Th1 responses, 2) the levels of many proinflammatory joint cytokines, and 3) serum levels of collagen‐reactive total IgG and IgG1, but not IgG2a and IgG3. Joint homogenate hemoglobin content was significantly reduced in CD6‐KO mice with CIA compared to WT mice with CIA (P < 0.05) (reduced angiogenesis). Moreover, treating CD6‐humanized mice with mouse anti‐human CD6 monoclonal antibody was similarly effective in reducing joint inflammation in CIA. Conclusion Taken together, these data suggest that interaction of CD6 with its ligands is important for the perpetuation of CIA and other inflammatory arthritides that are T cell driven.

show abstract

Synovial IL-9 facilitates neutrophil survival, function and differentiation of Th17 cells in rheumatoid arthritis

Cited by 53 publications

References 43 publications

Frequency of Th9 Cells in Different Stages of Rheumatoid Arthritis

Frequency of Th9 Cells in Different Stages of Rheumatoid Arthritis

Interleukin‐9 blockage reduces early hepatic granuloma formation and fibrosis during Schistosoma japonicum infection in mice

Attenuation of Murine Collagen‐Induced Arthritis by Targeting CD6

Contact Info

Product

Resources

About