IL-1b induces the rapid secretion of the antimicrobial protein IL-26 from Th17 cells

David I. Weiss, Feiyang Ma, Alexander A. Merleev, Emanual Michael Maverakis, Michel Gilliet, Samuel J. Balin, Bryan D. Bryson, Maria Teresa Ochoa, Matteo Pellegrini, Barry R. Bloom, Robert L. Modlin

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Th17 cells play a critical role in the adaptive immune response against extracellular bacteria, and the possible mechanisms by which they can protect against infection are of particular interest. In this study, we describe, to our knowledge, a novel IL-1b dependent pathway for secretion of the antimicrobial peptide IL-26 from human Th17 cells that is independent of and more rapid than classical TCR activation. We find that IL-26 is secreted 3 hours after treating PBMCs with Mycobacterium leprae as compared with 48 hours for IFN-g and IL-17A. IL-1b was required for microbial ligand induction of IL-26 and was sufficient to stimulate IL-26 release from Th17 cells. Only IL-1RI+ Th17 cells responded to IL-1b, inducing an NF-kB–regulated transcriptome. Finally, supernatants from IL-1b–treated memory T cells killed Escherichia coli in an IL-26–dependent manner. These results identify a mechanism by which human IL-1RI+ “antimicrobial Th17 cells” can be rapidly activated by IL-1b as part of the innate immune response to produce IL-26 to kill extracellular bacteria.

Original languageEnglish (US)
Pages (from-to)911-921
Number of pages11
JournalJournal of Immunology
Volume203
Issue number4
DOIs
StatePublished - Aug 15 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Weiss, D. I., Ma, F., Merleev, A. A., Maverakis, E. M., Gilliet, M., Balin, S. J., Bryson, B. D., Ochoa, M. T., Pellegrini, M., Bloom, B. R., & Modlin, R. L. (2019). IL-1b induces the rapid secretion of the antimicrobial protein IL-26 from Th17 cells. Journal of Immunology, 203(4), 911-921. https://doi.org/10.4049/jimmunol.1900318