The neutrophil antimicrobial peptide cathelicidin promotes Th17 differentiation

Danielle Minns, Katie J. Smith, Virginia Alessandrini, Gareth Hardisty, Lauren Melrose, Lucy Jackson-Jones, Andrew S. MacDonald, Donald J. Davidson and Emily Gwyer Findlay ()
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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

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21533-5

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DOI: 10.1038/s41467-021-21533-5

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