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

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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 substantial metabolic resources to fuel antibody production by tissue-resident plasma cells. Here, we demonstrate that 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 intestinal IgA + plasma cells, was found to exhibit rhythmicity. Oscillatory IgA responses were found to be entrained by time of feeding and were also found to be in part coordinated by the plasma cell-intrinsic circadian clock via deletion of the master clock gene Arntl. Moreover, reciprocal interactions between the host and microbiota dictated oscillatory dynamics among the commensal microbial community and its associated transcriptional and metabolic activity in an IgA-dependent manner. Together, our findings suggest that circadian networks comprising intestinal IgA, diet, and the microbiota converge to align circadian biology in the intestinal tract and to ensure host-microbial mutualism.

Original languageEnglish
Article numbereabk2541
JournalScience Immunology
Issue number75
Early online date2 Sept 2022
Publication statusE-pub ahead of print - 2 Sept 2022


  • Animals
  • Immunoglobulin A, Secretory
  • Intestines
  • Mammals
  • Microbiota
  • Periodicity
  • Symbiosis


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