Reciprocal regulation of IL-33 receptor–mediated inflammatory response and pulmonary fibrosis by TRAF6 and USP38 | Zendy

Xue-Mei Yi | Zendy; Mi Li | Zendy; Yun-Da Chen | Zendy; HongBing Shu | Zendy; Shu Li | Zendy

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Reciprocal regulation of IL-33 receptor–mediated inflammatory response and pulmonary fibrosis by TRAF6 and USP38

Author(s) -

Xue-Mei Yi,

Mi Li,

Yun-Da Chen,

HongBing Shu,

Shu Li

Publication year - 2022

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.2116279119

Subject(s) - ubiquitin ligase , ubiquitin , mechanism (biology) , pulmonary fibrosis , signal transduction , pathogenesis , inflammation , inflammatory response , immune system , bleomycin , autophagy , immunology , medicine , interleukin , biology , microbiology and biotechnology , lung , cytokine , genetics , apoptosis , gene , philosophy , epistemology , chemotherapy

Significance IL-33R mediates local inflammatory responses and plays crucial roles in the pathogenesis of immune diseases. In this study, we identified USP38, which negatively regulates IL-33-triggered signaling by mediating K27-linked deubiquitination of IL-33R at K511 and its autophagic degradation. USP38 deficiency aggravates IL-33–induced lung inflammatory response and bleomycin-induced pulmonary fibrosis. We further show that the E3 ubiquitin ligase TRAF6 catalyzes K27-linked polyubiquitination of IL-33R at K511, and that deficiency of TRAF6 inhibits IL-33–mediated signaling. Our findings reveal an important mechanism regarding how IL-33R is precisely regulated to ensure its inactivation in rest cells and proper activation following IL-33 stimulation.

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