Specific microbiota enhances intestinal IgA levels by inducing TGF‐β in T follicular helper cells of Peyer's patches in mice

Abstract

In humans and mice, mucosal immune responses are dominated by IgA antibodies and the cytokine TGF‐β, suppressing unwanted immune reactions but also targeting Ig class switching to IgA. It had been suggested that eosinophils promote the generation and maintenance of mucosal IgA‐expressing plasma cells. Here, we demonstrate that not eosinophils, but specific bacteria determine mucosal IgA production. Co‐housing of eosinophil‐deficient mice with mice having high intestinal IgA levels, as well as the intentional microbiota transfer induces TGF‐β expression in intestinal T follicular helper cells, thereby promoting IgA class switching in Peyer's patches, enhancing IgA+ plasma cell numbers in the small intestinal lamina propria and levels of mucosal IgA. We show that bacteria highly enriched for the genus Anaeroplasma are sufficient to induce these changes and enhance IgA levels when adoptively transferred. Thus, specific members of the intestinal microbiota and not the microbiota as such regulate gut homeostasis, by promoting the expression of immune‐regulatory TGF‐β and of mucosal IgA.

Prostaglandin E2 promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells

“…4d). Furthermore, Anaeroplasma bactoclasticum, which promotes expression of immune-regulatory TGF-β in the gut 37 , was also upregulated by indomethacin and reduced by the EP4 agonist ( Fig. 4d).…”

The Link between Oral and Gut Microbiota in Inflammatory Bowel Disease and a Synopsis of Potential Salivary Biomarkers

“…The extrinsic barrier at the intestinal epithelia includes mucus secretions, antibiotic peptides as well as various hormones, cytokines, chemokines, and commensal resident microbes [68]. Underlying the extrinsic barrier and epithelia is specialized gut-associated lymphoid tissue (GALT) [69]. GALT is the largest immune organ in the body and is the intestinal immune inductive site composed of scattered and isolated lymphoid follicles (ILFs), Peyer's patches [68], and mesenteric lymph nodes (MLNs) [69], containing immune cells including antigen presenting cells, macrophages, and B and T lymphocytes [70].…”

“…Underlying the extrinsic barrier and epithelia is specialized gut-associated lymphoid tissue (GALT) [69]. GALT is the largest immune organ in the body and is the intestinal immune inductive site composed of scattered and isolated lymphoid follicles (ILFs), Peyer's patches [68], and mesenteric lymph nodes (MLNs) [69], containing immune cells including antigen presenting cells, macrophages, and B and T lymphocytes [70]. The lamina propria is a secretory effector site where differentiated B cells from germinal centers residing under Peyer's patches are funneled into via lymphatics [71].…”

Beware of whom you live with: Your intestinal IgA may depend on it

“…Thus, it seems possible that the different mutant mice under study developed an intestinal microbiota composition that was distinct from the composition found in the WT mice, and that these altered microbiota were unable to maintain IgA + B cells in the intestine. In line with this view, the transfer of microbiota from WT or ΔdblGATA‐1 mice into WT mice, previously ‘emptied’ of bacteria by antibiotic treatment, induced an IgA high or an IgA low phenotype, respectively [9], indicating that eosinophilopenic mice can display an IgA high phenotype if they have an appropriate microbiota. Furthermore, the identification of Anaeroplasma as efficient IgA‐inducers, presumably through the activation of TGF‐β‐producing T FH cells, opens the door to mechanistic studies on how this particular bacterial genus is capable of such feats.…”

“…An article from this issue by Beller et al. [9] shows that a modified microbiota, rather than the absence of eosinophils in ΔdblGATA‐1 mice, leads to reduced numbers of IgA + GC B cells and IgA + plasma cells in the intestinal lamina propria, contradicting the earlier study [8]. They report that mutant mice co‐housed with WT littermates lose their characteristic low IgA phenotype, and that the transfer of microbiota from WT BALB/c to ΔdblGATA‐1 mice induced high levels of IgA.…”