Abstract 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. We here investigated whether B cell infiltration and their interaction with adipocytes influence inflammation and fibrosis of CD-associated adipose tissue. Analysing CrF of CD patients as well as WAT from a mouse model of intestinal inflammation, we found an accumulation of B cells and pro-fibrotic, M2-like macrophages. Depleting B cells through anti-CD20 antibody treatment diminished M2-like macrophage accumulation in inflamed mouse WAT. Mechanistically, we found that the B cell/adipocyte co-cultures led to elevated secretion of monocyte chemoattractant protein-1 (MCP-1) by primary adipocytes, in part due to TNF-a secretion by activated B cells. Adipocyte-derived MCP-1 resulted in enhanced macrophage migration. Furthermore, the supernatants of the B cell/adipocyte co-culture promoted pro-fibrotic, M2-like macrophage polarization in vitro , correlating with elevated levels of lactate. Single-cell RNA sequencing of human CrF and mouse WAT supported our in vitro findings suggesting that the B cell/adipocyte crosstalk supports a lactate-rich, inflammatory adipose tissue niche. Taken together, our results provide evidence for a crucial role of the B cell/adipocyte crosstalk to CD-associated adipose tissue inflammation. Graphical abstract One Sentence Summary B cells and pro-fibrotic macrophages accumulate in IBD-associated, inflamed adipose tissue B cell depletion in a mouse model reduces pro-fibrotic macrophage accumulation in IBD-associated, inflamed adipose tissue B cell/adipocyte crosstalk promotes B cell activation and MCP-1 secretion by adipocytes Adipocyte-derived MCP-1 promotes migration of macrophages B cell/adipocyte crosstalk provides a lactate-rich, inflammatory environment which likely drives pro-fibrotic macrophage polarisation
Goess et al. (Mon,) studied this question.