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IL-6 effector function of group 2 innate lymphoid cells (ILC2) is NOD2 dependent

journal contribution
posted on 2021-06-10, 13:02 authored by Clare S Hardman, Yi-Ling Chen, Maryam Salimi, Janina Nahler, Daniele Corridoni, Marta Jagielowicz, Chathuranga L Fonseka, David Johnson, Emmanouela Repapi, David J Cousins, Jillian L Barlow, Andrew NJ McKenzie, Alison Simmons, Graham Ogg
Cutaneous group 2 innate lymphoid cells (ILC2) are spatially and epigenetically poised to respond to barrier compromise and associated immunological threats. ILC2, lacking rearranged antigen-specific receptors, are primarily activated by damage-associated cytokines and respond with type 2 cytokine production. To investigate ILC2 potential for direct sensing of skin pathogens and allergens, we performed RNA sequencing of ILC2 derived from in vivo challenged human skin or blood. We detected expression of NOD2 and TLR2 by skin and blood ILC2. Stimulation of ILC2 with TLR2 agonist alone not only induced interleukin-5 (IL-5) and IL-13 expression but also elicited IL-6 expression in combination with Staphylococcus aureus muramyl dipeptide (MDP). Heat-killed skin-resident bacteria provoked an IL-6 profile in ILC2 in vitro that was notably impaired in ILC2 derived from patients with nucleotide-binding oligomerization domain-containing protein 2 (NOD2) mutations. In addition, we show that NOD2 signaling can stimulate autophagy in ILC2, which was also impaired in patients with NOD2 mutations. Here, we have identified a role for ILC2 NOD2 signaling in the differential regulation of ILC2-derived IL-6 and have reported a previously unrecognized pathway of direct ILC2 bacterial sensing.

History

Citation

Science Immunology 21 May 2021: Vol. 6, Issue 59, eabe5084 DOI: 10.1126/sciimmunol.abe5084

Author affiliation

Department of Respiratory Sciences, University of Leicester

Version

  • AM (Accepted Manuscript)

Published in

Science Immunology

Volume

6

Issue

59

Pagination

eabe5084

Publisher

American Association for the Advancement of Science (AAAS)

eissn

2470-9468

Copyright date

2021

Available date

2021-06-10

Language

en

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