4.6 Article

Identification of a Long Noncoding RNA TRAF3IP2-AS1 as Key Regulator of IL-17 Signaling through the SRSF10-IRF1-Act1 Axis in Autoimmune Diseases

Journal

JOURNAL OF IMMUNOLOGY
Volume 206, Issue 10, Pages 2353-2365

Publisher

AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.2001223

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Funding

  1. National Natural Science Foundation of China [81871280, 81770182]
  2. National Outstanding Youth Science Fund Project of National Natural Science Foundation of China [82022019]
  3. Natural Science Foundation of Shanghai [18ZR1435500]

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The study showed that TRAF3IP2-AS1 regulates IL-17A signaling by recruiting SRSF10, indicating a therapeutic potential for IL-17-related autoimmune diseases.
IL-17A plays an essential role in the pathogenesis of many autoimmune diseases, including psoriasis and multiple sclerosis. Act1 is a critical adaptor in the IL-17A signaling pathway. In this study, we report that an anti-sense long noncoding RNA, TRAF3IP2-AS1, regulates Act1 expression and IL-17A signaling by recruiting SRSF10, which downregulates the expression of IRF1, a transcriptional factor of Act1. Interestingly, we found that a psoriasis-susceptible variant of TRAF3IP2-AS1 A4165G (rs13210247) is a gain-of-function mutant. Furthermore, we identified a mouse gene E130307A14-Rik that is homologous to TRAF3IP2-AS1 and has a similar ability to regulate Act1 expression and IL-17A signaling. Importantly, treatment with lentiviruses expressing E130307A14-Rik or SRSF10 yielded therapeutic effects in mouse models of psoriasis and experimental autoimmune encephalomyelitis. These findings suggest that TRAF3IP2-AS1 and/or SRSF10 may represent attractive therapeutic targets in the treatment of IL-17-related autoimmune diseases, such as psoriasis and multiple sclerosis.

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