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NFAM1 promotes pro-inflammatory cytokine production in mouse and human monocytes.

ABSTRACT: NFAM1 is an ITAM bearing-transmembrane receptor. Based on overexpression studies, NFAM1 is reported to play a role in B cell signaling and development. We performed expression analysis of NFAM1 in publicly available gene expression data sets and discovered that NFAM1 expression is significantly induced in intestinal biopsies from Crohn’s disease (CD) and ulcerative colitis (UC) patients. At the cellular level, we observed high expression of NFAM1 in monocytes and neutrophils, in addition to expression in B and T cells. To explore the role of NFAM1 in multiple immune cells and its potential role in IBD, we generated NFAM1-/- mice. Contrary to previous reports using NFAM1-transgenic mice, NFAM1-/- mice have no obvious defects in immune cell development, or in T cell-dependent or independent B cell responses. Interestingly, NFAM1-/- monocytes produce reduced levels of TNF-α in response to activation by multiple IBD-relevant stimuli, including CD40L, TLR ligands and MDP. Collectively, these findings indicate that NFAM1 promotes pro-inflammatory monocyte development, thereby amplifying the response to diverse stimuli. These findings are not mouse-specific, as we found that deletion of NFAM1 in human monocytes also reduced expression of CD40L-induced CCL4.

ORGANISM(S): Mus musculus

PROVIDER: GSE188390 | GEO | 2022/01/03

REPOSITORIES: GEO

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