T follicular helper cell expansion and hyperimmunoglobulinemia with spontaneous IgE production to dietary antigens in IgA-deficient mice

Immunoglobulin A (IgA), the most abundantly produced antibody at mucosal surfaces, is thought to play key roles in immune responses to respiratory and enteric pathogens and in the regulation of commensal colonization. Low IgA levels have been associated with recurrent infections and immune dysregulation, including inflammatory bowel disease and autoimmunity. Levels of IgA in maternal breast milk and infant stool are both inversely associated with the emergence of immune responses to food antigens in infants and, in naturally resolving food sensitivity and immunotherapy protocols, the induction of IgA antibodies to dietary antigens has been associated with the acquisition of food tolerance. Here, we uncover new roles for IgA in intestinal immune homeostasis utilizing IgA Knockout (KO) mice generated by CRISPR/Cas9. IgA-deficient mice exhibit hyperimmunoglobulinemia, with increased levels of IgE and MCPT-1. The hyperimmunoglobulinemia is associated with dysregulated Tfh/Tfr responses in the Peyer’s Patches (PPs) and spontaneous immunoglobulin production to chow diet. These findings shed light on important interactions between IgA, the mucosal immune system, and the regulation of Tfh responses, emphasizing the importance of IgA in maintaining immune homeostasis at mucosal surfaces.