PRJNA788434
Mus musculus musculus Transcriptome or Gene expression
We found that expression of MANF was increased in colonic CD68+ macrophages of IBD patients and (DSS)-induced colitis model. Myeloid MANF deficiency was sufficient to exacerbate experimental colitis. Mice that received rhMANF showed significantly alleviation of colitis. MANF deficiency resulted in globally upregulated expression of pro-inflammatory cytokines and chemokines and increased the accumulation of CX3CR1int proinflammatory macrophages in inflamed colon tissues. We further demonstrate that MANF functions in macrophages as a negative regulator to control CHOP-BATF2-mediated inflammation, thereby protecting against colitis. Moreover, MANF also controls Th17-mediated immunopathology by inhibiting the production of CXCL9, CXCL10, CXCL11 and IL-12p40 in BATF2-mediated innate immune responses. In sum,our findings suggest that Macrophage-derived MANF contributes importantly to protect against inflammation and tissue injury in experimental colitis. Targeting MANF might represent a potential therapeutic approach for the treatment of intestinal inflammation.