Rhythmicity of Intestinal IgA Responses Confers Oscillatory Commensal Microbiota Mutualism

Hugo Penny, Rita Domingues, Maria Eduarda Zancanaro Krauss, Felipe Melo Gonzalez, Melissa Lawson, Suzanna Dickson, James Parkinson, Madeleine Hurry, Catherine Purse, Emna Jegham, Cristina Godinho-Silva, Miguel Rendas, Henrique Veiga-Fernandes, David Bechtold, Richard Grencis, Kai Michael Toellner, Ari Waisman, Jonathan Swann, Julie Gibbs, Matthew Hepworth

Research output: Contribution to journalArticlepeer-review


Interactions between the mammalian host and commensal microbiota are enforced through a range of immune responses that confer metabolic benefits and promote tissue health and homeostasis. Immunoglobulin A (IgA) responses directly determine the composition of commensal species that colonize the intestinal tract but require significant metabolic resources to fuel antibody production by tissue-resident plasma cells. Here we demonstrate IgA responses are subject to diurnal regulation over the course of a circadian day. Specifically, the magnitude of IgA secretion, as well as the transcriptome of tissue-resident IgA+ plasma cells, were found to exhibit rhythmicity. Oscillatory IgA responses were found to be entrained by time of feeding, and in-part coordinated by the plasma cell-intrinsic circadian clock. Moreover, reciprocal interactions between the host and microbiota dictated oscillatory dynamics amongst the commensal microbial community and its associated transcriptional and metabolic activity, in an IgA-dependent manner. Together our findings suggest circadian networks comprising intestinal IgA, the diet and the microbiota converge to align circadian biology in the intestinal tract and to ensure host-microbial mutualism.
Original languageEnglish
JournalScience Immunology
Publication statusAccepted/In press - 11 Aug 2022


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