T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?

Abstract

IntroductionA hallmark of systemic autoimmune diseases like systemic lupus erythematosus (SLE) is the increased expression of interferon (IFN) type I inducible genes, so-called IFN type I signature. Recently, T-helper 17 subset (Th17 cells), which produces IL-17A, IL-17F, IL-21, and IL-22, has been implicated in SLE. As CCR6 enriches for Th17 cells, we used this approach to investigate whether CCR6+ memory T-helper cells producing IL-17A, IL-17F, IL-21, and/or IL-22 are increased in SLE patients and whether this increase is related to the presence of IFN type I signature.MethodsIn total, 25 SLE patients and 15 healthy controls (HCs) were included. SLE patients were divided into IFN type I signature-positive (IFN+) (n = 16) and negative (IFN-) (n = 9) patients, as assessed by mRNA expression of IFN-inducible genes (IFIGs) in monocytes. Expression of IL-17A, IL-17F, IL-21, and IL-22 by CD4+CD45RO+CCR6+ T cells (CCR6+ cells) was measured with flow cytometry and compared between IFN+, IFN- patients and HCs.ResultsIncreased percentages of IL-17A and IL-17A/IL-17F double-producing CCR6+ cells were observed in IFN+ patients compared with IFN- patients and HCs. IL-17A and IL-17F expression within CCR6+ cells correlated significantly with IFIG expression. In addition, we found significant correlation between B-cell activating factor of the tumor necrosis family (BAFF)–a factor strongly correlating with IFN type I - and IL-21 producing CCR6+ cells.ConclusionsWe show for the first time higher percentages of IL-17A and IL-17A/IL-17F double-producing CCR6+ memory T-helper cells in IFN+ SLE patients, supporting the hypothesis that IFN type I co-acts with Th17 cytokines in SLE pathogenesis.

Interactions between Type 1 Interferons and the Th17 Response in Tuberculosis: Lessons Learned from Autoimmune Diseases

“…In support of this, IL-17 and Th17 cells are associated with disease severity in SLE to similar extent as T1-IFNs (20, 21, 241, 244). In turn, BAFF can promote Th17 responses (268, 269).…”

“…Th17 cells have been shown to be critical in the pathogenesis of MS and rheumatoid arthritis (RA) (19, 160). However, Th17 cells have also been associated with disease severity in AID characterized by a T1-IFN signature, such as systemic lupus erythematosus (SLE) (20, 233, 242, 243). Since T1-IFN signatures and Th17 responses are both associated with disease in AID, the question arises whether these two pathways act in concert to sustain and amplify autoimmune responses, or control each other (20, 21, 244).…”

Monocyte type I interferon signature in antiphospholipid syndrome is related to proinflammatory monocyte subsets, hydroxychloroquine and statin use

“…(A) Distribution of type I IFN scores among patients with SLE, SLE+APS and PAPS (means±95% CI). IFN scores were determined as previously described 12. Statistics: Analysis of variance (ANOVA) with post hoc Tukey's HSD.…”

Gene Expression Profiling in Peripheral Blood Cells and Synovial Membranes of Patients with Psoriatic Arthritis

“…Indeed coactivity of IFN and Th17 pathways is typical of autoimmunity and has been described both in human diseases and in animal models [18–20]. …”