Polyfunctional TEM cells in psoriatic arthritis synovium skewed towards Th17 cells

Raychaudhuri, Smriti K.; Abria, Christine; Raychaudhuri, S. P.

doi:10.1136/annrheumdis-2019-216658

Cited by 10 publications

(10 citation statements)

References 4 publications

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“…We have adopted the term polyfunctional from the work by others [35][36][37] acknowledging that this may be a suboptimal term as the production of cytokines is arguably a single function. MAIT cells have been shown to express several lineage transcription factors providing them with the capacity to produce multiple cytokines without following the Th1/Th2/Th17 paradigm.…”

Section: Discussionmentioning

confidence: 99%

Polyfunctional IL-17A+ MAIT cells are expanded in the peripheral blood of patients with HLA-B27+ axial spondyloarthritis

Lefton

Sharma

Patel

et al. 2022

Preprint

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Objectives: Studies in axial spondyloarthritis (axSpA) have yielded conflicting results regarding the identity of the major IL-17A-producing lymphocyte populations. The goal of this study was to comprehensively assess the production of IL-17A and related cytokines by peripheral blood lymphocytes in axSpA. Methods: Peripheral blood mononuclear cells were isolated from patients with axSpA and healthy controls matched for age, sex and HLA-B27 status. Unstimulated cells and cells activated with PMA/Ionomycin were analyzed by 25-parameter fluorescent flow cytometry. Data were analyzed by hierarchical gating, UMAP, and SPICE. Results: Except for a reduced frequency of mucosal-associated invariant T (MAIT) cells and natural killer (NK) cells, there were no other significant differences in abundance of major lymphocyte populations in axSpA patients compared with controls. Increased IL-17A production in axSpA was observed in total non-B lymphocytes and in MAIT cells. The fraction of MAIT cells expressing the tissue residency markers CD69 and CD103 was increased in axSpA. CD103 positive MAIT cells were enriched for IL-17A producers. axSpA patients demonstrated an expansion of MAIT cell subsets producing IL-17A, IL-17F, as well as GM-CSF and TNF. This expansion was only observed in HLA-B27+ patients. Conclusions: We document an expansion of polyfunctional IL-17A+ MAIT cells in the peripheral blood of HLA-B27+ patients with axSpA. These results are consistent with the implied role of intestinal dysbiosis or inflammation in axSpA pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Polyfunctional IL-17A+ MAIT cells are expanded in the peripheral blood of patients with HLA-B27+ axial spondyloarthritis

Lefton

Sharma

Patel

et al. 2022

Preprint

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“…Tyk2 and JAKs are recruited by multiple cytokines (Fig. 2) which influences several following possible functions of T cells which are required for immune-mediated inflammation in autoimmune disease [4,5,6 ▪▪ ,7–9,10 ▪ ,14,15]:…”

Section: Regulatory Role Of the Janus Kinase–signal Transducers And A...mentioning

confidence: 99%

“…Integrated interactions of antigen-presenting cells with T-cell phenotypes along with adhesion molecules, and lesional cytokines develop inflammatory proliferative cascades which lead to diverse clinical phenotypes for SpA [1,4,5]. The activated T cells regulate the local tissue response and damage through their cytokines and an integrated interaction with multiple inflammatory cells with innate functions such as macrophages and neutrophils [1,6 ▪▪ ,7,8]. It is also well-demonstrated that cytokines have crucial functions in the development, differentiation, and regulation of the immune cells.…”

Section: Introductionmentioning

confidence: 99%

Janus kinase–signal transducers and activators of transcription cell signaling in Spondyloarthritis: rationale and evidence for JAK inhibition

Raychaudhuri

Cheema

Raychaudhuri

2021

Current Opinion in Rheumatology

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Purpose of reviewThe Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling proteins represent a group of intracellular kinase molecules that play a central role in the signaling pathways induced by cytokines, chemokines, and certain growth factors associated with systemic and local inflammation of autoimmune diseases including in Spondyloarthritis (SpA). Here, we will discuss (i) the functional significance of the JAK-STAT kinase cascades in the inflammatory-proliferative processes of SpA and its cellular/molecular mechanisms (ii) progress in the development of oral synthetic JAK inhibitors (JAKi) and their therapeutic efficacies in SpA. Recent findingsDevelopment JAKi is a fast-moving field in the medical science. Several new-generation JAKi are being identified for psoriatic arthritis and ankylosing spondylitis. It is expected these JAKi likely to have higher potency and less adverse effects. SummaryHere, we are providing an updated review on the significance of JAK-STAT signaling proteins in SpA with an emphasis on new-generation of JAK-STAT inhibitors for the treatment of SpA.

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“…Th17 cells play a significant role in various autoimmune and inflammatory diseases [1,2]. Several recent studies link CD146 (MCAM-melanoma cell adhesion molecule) expression with Th17 effector function.…”

Section: Introductionmentioning

confidence: 99%

Phenotype and pathological significance of MCAM+ (CD146+) T cell subset in psoriatic arthritis

2021

Self Cite

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Background CD146 (MCAM-melanoma cell adhesion molecule) is a cell surface adhesion molecule for Laminin 411. T cells expressing MCAM are mainly responsible for IL-17 production. IL-17 secreting T helper cells (Th17 cells) are critical for the pathogenesis of psoriatic arthritis (PsA). Here we hypothesized enrichment of CD146+IL-17+ memory T cells in PsA synovium and studied the association of CD146 expression and CD4+IL-17+ activated memory (CD11a+CD45RO+) T cells in synovial fluid and blood of PSA, rheumatoid arthritis (RA, a positive control) and osteoarthritis (OA) patients. Methods Hi-D FACS studies were done to identify IL-17 in CD4+CD146+CD45RO+ and CD8+CD146+CD45RO+ T cells. Results We observed that effector CD146+(MCAM+) T cells are enriched at the synovial inflammation site in PsA. Conclusion As CD146+ T cells are a key resource for IL-17 it is likely that the enrichment of these MCAM+ pathologic cells are critical for the disease process of PsA.

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Polyfunctional TEM cells in psoriatic arthritis synovium skewed towards Th17 cells

Cited by 10 publications

References 4 publications

Polyfunctional IL-17A+ MAIT cells are expanded in the peripheral blood of patients with HLA-B27+ axial spondyloarthritis

Polyfunctional IL-17A+ MAIT cells are expanded in the peripheral blood of patients with HLA-B27+ axial spondyloarthritis

Janus kinase–signal transducers and activators of transcription cell signaling in Spondyloarthritis: rationale and evidence for JAK inhibition

Phenotype and pathological significance of MCAM+ (CD146+) T cell subset in psoriatic arthritis

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