The contribution from interleukin-27 towards rheumatoid inflammation: insights from gene expression

Millier, Melanie J; Lázaro, Kira; Stamp, Lisa K.; Hessian, Paul A.

doi:10.1038/s41435-020-0102-z

Cited by 10 publications

(9 citation statements)

References 34 publications

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“…The pathological mechanism of rheumatoid nodules has been identified as granulomas driven by Th1 cells (3). Recently, Millier et al determined that IL-27 levels in RA rheumatoid nodules are higher than that in RA synovial membranes and even higher than that in synovial membranes from end-stage RA (12). This means that rheumatoid arthritis might be a crucial source of IL-27 in RA.…”

Section: Sources and Signaling Pathways Of Il-27mentioning

confidence: 99%

“…Studies comparing IL-27 levels in the joint cavity between RA and OA are lacking. However, increased IL-27 levels have been detected in both RA synovial membranes and synovial fluids compared to OA tissues ( 11 , 12 ). Moreover, mRNA expression of the IL-27 receptor is also increased in RA synovial membranes.…”

Section: Il-27 Is Related To the Progression Of Ramentioning

confidence: 99%

“…Increased IL-27 levels indicate that there are correlations between IL-27 and RA, meaning that the IL-27 signaling pathway might contribute to synovitis in RA. However, the possibility cannot be ruled out that IL-27 might be an innocent bystander in RA ( 12 ).…”

Section: Il-27 Is Related To the Progression Of Ramentioning

confidence: 99%

“…An association between IL-27 single-nucleotide polymorphisms (SNPs) and genetic susceptibility to RA has been described (9). Abnormal IL-27 levels have been well demonstrated in previous studies, and IL-27 participates in RA development via multiple pathways (10)(11)(12). Earlier studies found that IL-27 primarily affects the differentiation of helper T cell subsets (13).…”

Section: Introductionmentioning

confidence: 98%

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Interleukin 27 Signaling in Rheumatoid Arthritis Patients: Good or Evil?

Liang

Chen

et al. 2022

Front. Immunol.

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The occurrence and development of rheumatoid arthritis (RA) is regulated by numerous cytokines. Interleukin 27 (IL-27) is a soluble cytokine that exerts biological effects by regulating the Janus tyrosine kinase (JAK)/signal transducer and activator of the transcription (STAT) signaling pathway via the IL-27 receptor. IL-27 is known for its pleiotropic roles in modulating inflammatory responses. Previous studies found that IL-27 levels are elevated in RA blood, synovial fluid, and rheumatoid nodules. Cellular and animal experiments indicated that IL-27 exerts multiple regulatory functions in RA patients via different mechanisms. IL-27 inhibits ectopic-like structure (ELS) formation and CD4+ T helper type 2 (Th2) cell, CD4+ T helper type 17 (Th17) cell, and osteoclast differentiation in RA, contributing to alleviating RA. However, IL-27 promotes Th1 cell differentiation, which may exacerbate RA synovitis. Moreover, IL-27 also acts on RA synovial fibroblasts (RA-FLSs) and regulatory T cells (Tregs), but some of its functions are unclear. There is currently insufficient evidence to determine whether IL-27 promotes or relieves RA. Targeting IL-27 signaling in RA treatment should be deliberate based on current knowledge.

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Section: Sources and Signaling Pathways Of Il-27mentioning

confidence: 99%

Section: Il-27 Is Related To the Progression Of Ramentioning

confidence: 99%

Section: Il-27 Is Related To the Progression Of Ramentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Interleukin 27 Signaling in Rheumatoid Arthritis Patients: Good or Evil?

Liang

Chen

et al. 2022

Front. Immunol.

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“…IL‐27 was also detected in nodules of RA patients. However, the effect of nodule‐derived IL‐27 on the systemic or synovial inflammation in RA remains unknown [18]. In recent researches, some studies showed that IL‐27 could ameliorate arthritis mainly through suppressing IL‐17‐mediated inflammation, exhibiting a protective role in RA [19].…”

Section: Introductionmentioning

confidence: 99%

Altered peripheral B lymphocyte homeostasis and functions mediated by IL‐27 via activating the mammalian target of rapamycin signaling pathway in patients with rheumatoid arthritis

Tang

Bai

et al. 2021

Clin Exp Immunol

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B cell dysfunction and inflammatory cytokine over‐production participate in the pathogenesis of rheumatoid arthritis (RA). Here we compared peripheral B cell homeostasis and immune functions between RA patients and healthy controls (HC) and explored vital signaling pathways involved in altered RA B cells. We found that RA patients showed significantly decreased frequencies of peripheral CD19+CD27+CD24high regulatory B (Breg) cells but increased frequencies of CD19+CD27+CD38high plasmablasts and CD19+CD138+ plasma cells, and higher levels of serum immunoglobulin (Ig)M and IgG. Compared to HC peripheral B cells, RA peripheral B cells had more increased proliferation and higher expression of activation markers. Importantly, our results showed that RA peripheral B cells displayed the mTOR signaling pathway to be more activated, and inhibition of mTOR could restore RA B cell homeostasis and functions. RA serum‐treated B cells exhibited more increased expressions of mTOR, which could be restored with the addition of anti‐interleukin (IL)‐27 neutralizing antibody. Serum IL‐27 levels were significantly increased in RA patients and positively correlated with disease activity, the frequencies of plasma cells and the levels of autoantibodies. In vitro, IL‐27 notably promoted immune dysfunction of RA B cells, which were inhibited by anti‐IL‐27 neutralizing antibody. Also, the mTOR pathway was more activated in IL‐27‐treated RA B cells, and mTOR inhibition apparently reversed abnormalities of RA B cells mediated by IL‐27. These results suggest that increased serum IL‐27 levels could promote peripheral B cell dysfunction in RA patients via activating the mTOR signaling pathway. Thus, IL‐27 may play a pro‐pathogenic role in the development of RA, and antagonizing IL‐27 could be a novel therapy strategy for RA.

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