Apyrase-mediated amplification of secretory IgA promotes intestinal homeostasis

• Published in: Cell reports (Cambridge) Vol. 40; no. 3; p. 111112
• Main Authors: Perruzza, Lisa, Strati, Francesco, Raneri, Matteo, Li, Hai, Gargari, Giorgio, Rezzonico-Jost, Tanja, Palatella, Martina, Kwee, Ivo, Morone, Diego, Seehusen, Frauke, Sonego, Paolo, Donati, Claudio, Franceschi, Pietro, Macpherson, Andrew J., Guglielmetti, Simone, Greiff, Victor, Grassi, Fabio
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 19.07.2022; Cell Press
• Subjects: dysbiosis; extracellular ATP; microbiota; purinergic signaling; secretory IgA; T follicular helper cell; microbiota; CP: Immunology; purinergic signaling; secretory IgA; T follicular helper cell; dysbiosis; extracellular ATP
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.111112

Secretory immunoglobulin A (SIgA) interaction with commensal bacteria conditions microbiota composition and function. However, mechanisms regulating reciprocal control of microbiota and SIgA are not defined. Bacteria-derived adenosine triphosphate (ATP) limits T follicular helper (Tfh) cells in the Peyer’s patches (PPs) via P2X7 receptor (P2X7R) and thereby SIgA generation. Here we show that hydrolysis of extracellular ATP (eATP) by apyrase results in amplification of the SIgA repertoire. The enhanced breadth of SIgA in mice colonized with apyrase-releasing Escherichia coli influences topographical distribution of bacteria and expression of genes involved in metabolic versus immune functions in the intestinal epithelium. SIgA-mediated conditioning of bacteria and enterocyte function is reflected by differences in nutrient absorption in mice colonized with apyrase-expressing bacteria. Apyrase-induced SIgA improves intestinal homeostasis and attenuates barrier impairment and susceptibility to infection by enteric pathogens in antibiotic-induced dysbiosis. Therefore, amplification of SIgA by apyrase can be leveraged to restore intestinal fitness in dysbiotic conditions. [Display omitted] •Extracellular ATP modulates the secretory IgA (SIgA) response in the intestine•Delivery of the ATP-degrading enzyme apyrase amplifies the breadth of SIgA repertoire•Enhanced SIgA coating of the microbiota by apyrase conditions enterocyte function•Enhanced SIgA coating of the microbiota preserves gut integrity during dysbiosis Secretory IgA plays pleiotropic function in ensuring the integrity of the intestinal ecosystem. Perruzza et al. show that amplification of gut SIgA repertoire by hydrolysis of endoluminal extracellular ATP can condition enterocyte transcriptional activity and promote intestinal homeostasis and colonization resistance in dysbiosis.