Adiponectin Enhances B-Cell Proliferation and Differentiation via Activation of Akt1/STAT3 and Exacerbates Collagen-Induced Arthritis.
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ABSTRACT:
SUBMITTER: Che N
PROVIDER: S-EPMC8012765 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Erythroid differentiation regulator 1 (Erdr1) has been identified as an anti-inflammatory factor in several disease models, including collagen-induced arthritis (CIA), but its exact mechanisms are still not fully understood. Here, the involvement of regulatory T (Treg) cells in Erdr1-improved CIA was investigated. In the CIA model, Erdr1 was confirmed to reduce collagen-specific IgM in plasma and plasma cells in draining lymph nodes. Importantly, the downregulated Treg cell ratio in draining lymph nodes from CIA mice was recovered by Erdr1 treatment. In addition, administration of Erdr1 improved the CIA score and joint tissue damage, while it revealed no effect in Treg cell-depleted CIA mice, indicating that Treg cells mediate the therapeutic effects of Erdr1 in the CIA model. Results from in vitro experiments also demonstrated that Erdr1 significantly induced Treg cell differentiation and the expression of Treg activation markers, including CD25, CD69, and CTLA4 in CD4+Foxp3+ cells. Furthermore, Erdr1-activated Treg cells dramatically suppressed the proliferation of responder T cells, suggesting that they are functionally active. Taken together, these results show that Erdr1 induces activation of Treg cells and ameliorates rheumatoid arthritis via Treg cells.
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Project description:Sepsis is a multifactorial, and often fatal, disorder typically characterized by widespread inflammation and immune activation with resultant endothelial activation. In the present study, we postulated that the adipokine adiponectin serves as a critical modulator of survival and endothelial activation in sepsis. To this aim, we evaluated both loss-of-function (adiponectin gene-deficient mice) and subsequent gain-of-function (recombinant adiponectin reconstitution) strategies in two well-established inflammatory models, cecal ligation perforation (CLP) and thioglyocollate-induced peritonitis. Adipoq(-/-) mice, subjected to CLP, exhibited a profound ( approximately 8-fold) reduction in survival compared with their wild-type Adipoq(+/+) littermates after 48 h. Furthermore, compared with wild-type controls, thioglycollate challenge resulted in a markedly greater influx of peritoneal neutrophils in Adipoq(-/-) mice accompanied by an excess production of key chemoattractant cytokines (IL-12p70, TNFalpha, MCP-1, and IL-6) and upregulation of aortic endothelial adhesion molecule VCAM-1 and ICAM-1 expressions. Importantly, all of these effects were blunted by recombinant total adiponectin administration given 3 days prior to thioglycollate challenge. The protective effects of adiponectin were ascribed largely to higher-order adiponectin oligomers, since administration of recombinant C39A trimeric adiponectin did not attenuate endothelial adhesion molecule expression in thioglycollate-challenged Adipoq(-/-) mice. These data suggest a critical role of adiponectin as a modulator of survival and endothelial inflammation in experimental sepsis and a potential mechanistic link between adiposity and increased sepsis.
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