The secretory IgA response in the intestine and host’s systemic metabolism
Research area: Mucosal Immunology
Group leaders: Fabio Grassi
- Lisa Perruzza, Scientist
Status: In progress
The secretory immunoglobulin A (SIgA) in mammalian gut protects the organism from infections and contributes to host physiology by shaping microbiota composition. The mechanisms regulating the adaptive SIgA response towards gut microbes are poorly defined. Deletion of the P2rx7 gene, encoding for the adenosine triphosphate (ATP)-gated ionotropic P2X7 receptor, leads to T follicular helper (Tfh) cells expansion in the Peyer’s patches (PPs) of the small intestine, enhanced germinal centre (GC) reaction and IgA secretion; the resulting alterations of the gut microbiota in turn affects host metabolism. We have defined gut microbiota modifications that correlate with deregulated SIgA secretion and metabolic alterations in P2rx7-/- mice. In particular, Lactobacillus showed enhanced SIgA coating in P2rx7-/- with respect to wild-type (WT) mice, suggesting Lactobacillus-specific SIgA response conditioned host metabolism. Accordingly, oral administration of intestinal Lactobacillus isolates from P2rx7-/- mice to WT animals resulted in altered glucose homeostasis and fat deposition. We are pursuing the hypothesis that microbiota derived ATP could condition host metabolism via P2X7 regulated sIgA coating of commensals.