Glycosylation of mucosal B cells modulates gut inflammation as a result of cytokine imbalance

CUTINE AM; CAGNONI AJ; GATTO S; TOSCANO MA; MANSELLE COCCO MN; MORALES R; RABINOVICH GA; MOROSI L; MARTINEZ ALLO V; MAY M; MARIÑO KV

Congreso; International Congress of Mucosal Immunology 2019; 2019

The glycome of immune cells is a key regulator of cellular processes relevant to health and disease.It has been shown that development of inflammation alters T cell glycosylation contributing to theexacerbation of inflammatory bowel diseases (IBD). However, the glycome of other immune cellsduring colitis remains poorly described. Here, we demonstrate that chronic inflammation alters Blymphocyte and plasma cell glycosylation, negatively affecting their tolerogenic role during colitis.We observed that the glycome of colonic B cells and IgA + plasma cells (PCs) from mice coursingDSS-induced chronic colitis presented lower levels of surface α2,6-sialylation (α2,6sia). Toinvestigate the consequences of this alteration we co-transferred into RAG2 -/- mice colitogenic-CD4 + CD45RB hi T cells with B cells isolated from either WT or ST6Gal1 deficient animals (ST6Gal1 -/-), a glycosyltransferase that adds α2,6sia to N-glycans. While co-transfer with WT B cells reducedcolonic T cell infiltration, co-transfering with ST6Gal1 -/- B cells resulted in higher inflammation thantheir WT counterparts and lower amounts of both fecal IgA and PCs. To identify potential mediatorsinvolved in the regulation of α2,6sia we differentiated IgA PCs and incubated them with a panel ofcytokines. We found that IFN-γ, IL-4 and IL-21 induce α2,6sia on IgA + cells. Considering that IL-4levels are reduced in our colitis model, we propose that downregulation of this cytokine could be inpart responsible for the decrease in α2,6sia on PCs during colitis. Collectively, our results suggestthat α2,6sia exerts a regulatory role on B cells during IBD and provide a potential mechanism forthe modulation of B cell functionality on inflamed intestinal tissues.