B cell/adipocyte crosstalk amplifies MCP-1 secretion, M2-like macrophage accumulation, and polarization in gut-associated, inflamed adipose tissue 

ABSTRACT

BACKGROUND AND AIMS: During Crohn's disease (CD), hyperplasia of the mesenteric white adipose tissue (WAT), called creeping fat (CrF), is associated with the accumulation of immune cells. Here we investigated the impact of B cell/adipocyte crosstalk on immune cell recruitment and inflammation within inflammatory bowel disease-related adipose tissue.

METHODS: We used flow cytometry and in vitro 3D culture systems of biopsies from CrF of CD patients as well as a mouse model of intestinal inflammation, in vitro co-cultures, mass spectrometry, and single-cell RNA sequencing to evaluate the impact of B cell/adipocyte interplay on monocyte chemoattractant protein-1 (MCP-1) production and macrophage polarization.

RESULTS: Employing primary human and mouse 3D adipocyte cultures, we observed that adipocytes from CD patients displayed a persistent inflammatory phenotype even after prolonged time in culture, a cytokine secretion profile also recapitulated via lipopolysaccharide stimulation. Analyzing CrF of CD patients as well as WAT of a mouse model of intestinal inflammation, we found an accumulation of B cells. B cell/adipocyte co-cultures led to elevated secretion of MCP-1 by primary adipocytes, facilitating macrophage migration. Consequently, co-transfer of B cells with T cells increased T cell activation and M2-like macrophage accumulation in inflamed mouse WAT. Mass spectrometry and single-cell RNA sequencing analyses suggested that the B cell/adipocyte crosstalk establishes a microenvironment that may promote M2-like macrophage polarization.

CONCLUSION: B cell/adipocyte interactions in CD-associated inflamed adipose tissue increase MCP-1 and lactate, promoting recruitment and M2-like polarization of macrophages, likely amplifying local WAT inflammation.

PMID:42998367 | PMC:PMC13744403 | DOI:10.1093/ecco-jcc/jjag182

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