Nod2 Deficiency Augments Th17 Responses and Exacerbates Autoimmune Arthritis.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Ruth J NapierHolly L Rosenzweig

Abstract

Arthritis in a genetically susceptible SKG strain of mice models a theoretical paradigm wherein autoimmune arthritis arises because of interplay between preexisting autoreactive T cells and environmental stimuli. SKG mice have a point mutation in ZAP-70 that results in attenuated TCR signaling, altered thymic selection, and spontaneous production of autoreactive T cells that cause arthritis following exposure to microbial β-glucans. In this study, we identify Nod2, an innate immune receptor, as a critical suppressor of arthritis in SKG mice. SKG mice deficient in Nod2 (Nod2-/-SKG) developed a dramatically exacerbated form of arthritis, which was independent of sex and microbiota, but required the skg mutation in T cells. Worsened arthritis in Nod2-/-SKG mice was accompanied by expansion of Th17 cells, which to some measure coproduced TNF, GM-CSF, and IL-22, along with elevated IL-17A levels within joint synovial fluid. Importantly, neutralization of IL-17A mitigated arthritis in Nod2-/-SKG mice, indicating that Nod2-mediated protection occurs through suppression of the Th17 response. Nod2 deficiency did not alter regulatory T cell development or function. Instead, Nod2 deficiency resulted in an enhanced fundamental ability of S...Continue Reading

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Citations

Jun 7, 2019·Clinical Reviews in Allergy & Immunology·Carlo Selmi
Mar 19, 2020·American Journal of Physiology. Cell Physiology
Feb 17, 2021·Acta Pharmacologica Sinica·Li ChenJian-Ping Zuo

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