IL-38, a potential therapeutic agent for lupus, inhibits lupus progression View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2022-07-01

AUTHORS

Wang-Dong Xu, Lin-Chong Su, Lu Fu, You-Yu Lan, Xiao-Yan Liu, Qi Huang, Qian Wu, Jie Zhou, An-Fang Huang

ABSTRACT

BackgroundPrevious studies reported that IL-38 was abnormally expressed in patients with systemic lupus erythematosus (SLE). However, the involvement of IL-38 in the pathophysiology of SLE remains unknown.MethodsThe therapeutic potential of IL-38 was tested in pristane-treated wild-type (WT) and IL-38−/− mice. Thus, SLE was induced via pristane in WT and IL-38−/− mice. Afterwards, the liver, spleen, and kidney of each mouse were obtained. The flow cytometric analysis of the immune cells, serologic expression of inflammatory cytokines and autoantibodies, renal histopathology, and inflammatory signaling were evaluated.ResultsWT mice with pristane-induced lupus exhibited hepatomegaly, splenomegaly, severe kidney damages, increased lymphoproliferation, enhanced lymphoproliferation, and upregulated inflammatory cytokines, such as IL-6, IL-13, IL-17A, MIP-3α, IL-12p70, and IFNγ, and elevated levels of autoantibodies, such as ANA IgG, anti-dsDNA IgG, and total IgG. IL-38−/− mice whose lupus progressed, had elevated cells of CD14+, CD19+, CD3+, and Th1, upregulated inflammatory cytokines and autoantibodies, and severe pathological changes in kidney. Administration of recombinant murine IL-38 to pristane-treated IL-38−/− mice improved their renal histopathology, which depended on ERK1/2, JNK1/2, p38, NF-κB p65, and STAT5 signaling pathways.ConclusionIL-38 regulates SLE pathogenesis. Furthermore, targeting IL-38 is critical in the treatment of SLE. More... »

PAGES

963-975

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00011-022-01581-3

DOI

http://dx.doi.org/10.1007/s00011-022-01581-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1149152658

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/35776155


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