IgA and Intestinal Homeostasis

Mucosal immunity in a healthy gut

“…35,87 Importantly, bacterial overgrowth occurs in the jejunum of vagotomized patients only when IgA deficiency is combined with suboptimal function of innate defenses such as gastric acid and peristalsis. 45,88 In this context, it is notable that the frequency of selective IgA deficiency among patients with Crohn's disease in Sweden is significantly increased, that is, one in 100 compared to one in 600 for the healthy population (Lennart Hammarström, personal communication).…”

“…105 The mucosal clearance function exhibited by pIgA (and probably pentameric IgM) antibodies reinforces the immune exclusion mediated by SIgA (and SIgM) with innate-like low-affinity antibody activity generated against commensal bacteria, and which to some extent may be cross-reactive. 8,45,106 The high-affinity antibodies induced by pathogens or properly adjuvanted oral vaccines may contribute even more efficiently to both immune exclusion and mucosal clearance, as reviewed elsewhere. 5 Locally produced pIgA may further influence homeostasis by interacting with the Fcα receptor (FcαRI, CD89) on leukocytes in the lamina propria.…”

“…97,128 Cell culture experiments with the polarized human colon carcinoma cell line HT-29 have shown that ligation of TLR3 and TLR4 with the respective MAMPs (double-stranded RNA and LPS) from the apical side upregulates pIgR expression, 129 which may then increase the pIg export and thus enhance secretory immunity. 45,130 Gut bacteria of the family Enterobacteriaceae can induce this effect. 131…”

“…8,45 Thus, experiments have revealed a role of the important PRRs designated Toll-like receptors (TLRs) for B-cell differentiation in GALT. 8,45 Interestingly, human GALT follicles contain the apparatus to support both T celldependent and T cell-independent (not involving CD40-CD40L/CD154 interactions) class switch recombination (CSR) pathways to IgA. 46,47 This has been documented by showing GALT-restricted human expression of activation-induced cytidine deaminase (AID) -an essential enzyme for CSR to take place.…”

“…69 Immune exclusion is therefore normally performed mainly by SIgA in cooperation with innate defenses such as mucus, defensins and peristalsis. 2,45 In newborns and subjects with selective IgA deficiency, however, SIgM antibodies are of greater importance than in healthy adults. 29,35 Thus, IgA is generally undetectable in the mucosa before 10 days of age, and IgM + PCs often remain predominant up to one month.…”