An Accord of Nuclear Receptor Expression in CD4 T Cells in Rheumatoid Arthritis.

Saini, Ankita and Mahajan, Sahil and Bhagyaraj, Ella and Kalra, Rashi and Nanduri, Ravikanth and Gupta, Ravi and Khatri, Neeraj and Gupta, Pawan (2019) An Accord of Nuclear Receptor Expression in CD4 T Cells in Rheumatoid Arthritis. ImmunoHorizons, 3 (8). pp. 402-411. ISSN 2573-7732

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Chronically activated CD4 T cells drive uncontrolled inflammation, leading to tissue damage in various autoimmune disorders, such as rheumatoid arthritis (RA). Investigation of the molecular mechanisms involved in RA and recent analysis of transcriptomic profiles has implicated members of the nuclear receptor (NR) superfamily in RA. NRs are required for the development, differentiation, and effector function of CD4 T cells; therefore, it is thought that NRs are important in shaping the CD4 T cell repertoire and associated inflammation in RA. Despite their relevance, the full potential of the NR superfamily in RA, either as biomarkers or disease targets, has not been harnessed. To gain insight on the NR members that are closely associated with RA disease activity, we generated an expression atlas for the NR superfamily in CD4 T cells isolated either in a steady state or over the course of collagen-induced arthritis mouse model of RA. We observed discrete expression patterns among the NR superfamily during the disease stages. NRs that instigate anti-inflammatory programs underwent major downregulation during disease onset; however, during the fully developed disease stage we noticed that NRs that induce proinflammatory programs had reduced transcript levels. These animal findings corroborated well with the expression patterns of NRs in clinical samples obtained from RA patients. Furthermore, we observed that targeting NRs using synthetic ligands alleviates the progression of collagen-induced arthritis. Overall, our data demonstrates the potential of the NR superfamily as novel therapeutic targets for the treatment of autoimmune disorders.

Item Type: Article
Additional Information: Copyright of this article belongs to AAI.
Subjects: Q Science > QR Microbiology
Depositing User: Dr. K.P.S.Sengar
Date Deposited: 12 Dec 2019 10:10
Last Modified: 12 Dec 2019 10:10

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