Microbiota Sensing by Mincle-Syk Axis in Dendritic Cells Regulates Interleukin-17 and -22 Production and Promotes Intestinal Barrier Integrity

María Martínez-López, Salvador Iborra, Ruth Conde-Garrosa, Annalaura Mastrangelo, Camille Danne, Elizabeth R Mann, Delyth M Reid, Valérie Gaboriau-Routhiau, Maria Chaparro, María P Lorenzo, Lara Minnerup, Paula Saz-Leal, Emma Slack, Benjamin Kemp, Javier P Gisbert, Andrzej Dzionek, Matthew J Robinson, Francisco J Rupérez, Nadine Cerf-Bensussan, Gordon D BrownDavid Bernardo, Salomé LeibundGut-Landmann, David Sancho

Research output: Contribution to journalArticle

25 Citations (Scopus)
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Abstract

Production of interleukin-17 (IL-17) and IL-22 by T helper 17 (Th17) cells and group 3 innate lymphoid cells (ILC3s) in response to the gut microbiota ensures maintenance of intestinal barrier function. Here, we examined the mechanisms whereby the immune system detects microbiota in the steady state. A Syk-kinase-coupled signaling pathway in dendritic cells (DCs) was critical for commensal-dependent production of IL-17 and IL-22 by CD4+ T cells. The Syk-coupled C-type lectin receptor Mincle detected mucosal-resident commensals in the Peyer's patches (PPs), triggered IL-6 and IL-23p19 expression, and thereby regulated function of intestinal Th17- and IL-17-secreting ILCs. Mice deficient in Mincle or with selective depletion of Syk in CD11c+ cells had impaired production of intestinal RegIIIγ and IgA and increased systemic translocation of gut microbiota. Consequently, Mincle deficiency led to liver inflammation and deregulated lipid metabolism. Thus, sensing of commensals by Mincle and Syk signaling in CD11c+ cells reinforces intestinal immune barrier and promotes host-microbiota mutualism, preventing systemic inflammation.

Original languageEnglish
Pages (from-to)446-461
Number of pages15
JournalImmunity
Volume50
Issue number2
Early online date29 Jan 2019
DOIs
Publication statusPublished - 19 Feb 2019

Keywords

  • intestinal barrier
  • dendritic cell
  • T lymphocyte
  • innate lymphoid cells
  • Minkle
  • Syk kinase
  • IL-17
  • IL-22
  • antimicrobial defense
  • gut microbiota translocation
  • liver inflammation
  • lipid metabolism
  • Mincle
  • IGA
  • C-TYPE LECTIN
  • COMMENSAL BACTERIA
  • ROR-GAMMA-T
  • PEYERS-PATCHES
  • INDUCTION
  • INNATE LYMPHOID-CELLS
  • ADAPTIVE IMMUNITY
  • T(H)17 CELLS
  • DIFFERENTIATION

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy
  • Immunology

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    Martínez-López, M., Iborra, S., Conde-Garrosa, R., Mastrangelo, A., Danne, C., Mann, E. R., Reid, D. M., Gaboriau-Routhiau, V., Chaparro, M., Lorenzo, M. P., Minnerup, L., Saz-Leal, P., Slack, E., Kemp, B., Gisbert, J. P., Dzionek, A., Robinson, M. J., Rupérez, F. J., Cerf-Bensussan, N., ... Sancho, D. (2019). Microbiota Sensing by Mincle-Syk Axis in Dendritic Cells Regulates Interleukin-17 and -22 Production and Promotes Intestinal Barrier Integrity. Immunity, 50(2), 446-461. https://doi.org/10.1016/j.immuni.2018.12.020