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The neutrophil antimicrobial peptide cathelicidin promotes Th17 differentiation

Author

Listed:
  • Danielle Minns

    (University of Edinburgh; 47 Little France Crescent)

  • Katie J. Smith

    (University of Edinburgh; 47 Little France Crescent)

  • Virginia Alessandrini

    (University of Edinburgh; 47 Little France Crescent)

  • Gareth Hardisty

    (University of Edinburgh; 47 Little France Crescent)

  • Lauren Melrose

    (University of Edinburgh; 47 Little France Crescent)

  • Lucy Jackson-Jones

    (Lancaster University)

  • Andrew S. MacDonald

    (University of Manchester)

  • Donald J. Davidson

    (University of Edinburgh; 47 Little France Crescent)

  • Emily Gwyer Findlay

    (University of Edinburgh; 47 Little France Crescent)

Abstract

The host defence peptide cathelicidin (LL-37 in humans, mCRAMP in mice) is released from neutrophils by de-granulation, NETosis and necrotic death; it has potent anti-pathogen activity as well as being a broad immunomodulator. Here we report that cathelicidin is a powerful Th17 potentiator which enhances aryl hydrocarbon receptor (AHR) and RORγt expression, in a TGF-β1-dependent manner. In the presence of TGF-β1, cathelicidin enhanced SMAD2/3 and STAT3 phosphorylation, and profoundly suppressed IL-2 and T-bet, directing T cells away from Th1 and into a Th17 phenotype. Strikingly, Th17, but not Th1, cells were protected from apoptosis by cathelicidin. We show that cathelicidin is released by neutrophils in mouse lymph nodes and that cathelicidin-deficient mice display suppressed Th17 responses during inflammation, but not at steady state. We propose that the neutrophil cathelicidin is required for maximal Th17 differentiation, and that this is one method by which early neutrophilia directs subsequent adaptive immune responses.

Suggested Citation

  • Danielle Minns & Katie J. Smith & Virginia Alessandrini & Gareth Hardisty & Lauren Melrose & Lucy Jackson-Jones & Andrew S. MacDonald & Donald J. Davidson & Emily Gwyer Findlay, 2021. "The neutrophil antimicrobial peptide cathelicidin promotes Th17 differentiation," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21533-5
    DOI: 10.1038/s41467-021-21533-5
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