RCAN1 deficiency protects againstSalmonellaintestinal infection by modulating JNK activation

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HighlightsRCAN1 suppresses the intestinal inflammation during acute Salmonella infection.RCAN1 negatively regulates the intestinal inflammatory response by dampening JNK activation.RCAN1 deficiency promotes pathogen clearance and improves host survival following Salmonella challenge.Intervention of RCAN1 signaling may aid in our therapeutic efforts to prevent and treat salmonellosis.Objective:RCAN1 (regulator of calcineurin 1) has been shown to be involved in various physiological and pathological processes. However, the biological implications of RCAN1 during gastrointestinal tract infection remain unclear. In this study, we tried to determine the role of RCAN1 in acute Salmonella infectious colitis.Methods:Wild type and RCAN1-deficient mice or macrophages were used to characterize the impacts of RCAN1 on intestinal inflammation, inflammatory cytokines production, animal survival, and pathogen clearance following Salmonella challenge.Results:Histologic and quantitative assessments showed increased inflammation and elevated proinflammatory cytokines production in RCAN1-deficient mice. The aberrant inflammatory response was recapitulated in primary bone marrow-derived macrophages. In addition, we reveal a novel regulatory role for RCAN1 in the proinflammatory JNK signaling both in vitro and in vivo. Further analysis showed that the increased inflammation in RCAN1-deficient mice contributed to pathogen clearance and host survival.Conclusions:The present study demonstrates that RCAN1 deficiency protects against Salmonella intestinal infection by enhancing proinflammatory JNK signaling.

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