Journal article
IL-6 effector function of group 2 innate lymphoid cells (ILC2) is NOD2 dependent
- Abstract:
- Cutaneous group 2 innate lymphoid cells (ILC2) are spatially and epigenetically poised to respond to barrier compromise and associated immunological threats. ILC2, lacking rearranged antigenspecific receptors, are primarily activated by damage-associated cytokines and respond with type2 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 induced 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 strikingly impaired in ILC2 derived from patients with NOD2 mutations. In addition, we show 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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-
(Preview, Accepted manuscript, pdf, 3.9MB, Terms of use)
-
- Publisher copy:
- 10.1126/sciimmunol.abe5084
Authors
- Publisher:
- American Association for the Advancement of Science
- Journal:
- Science Immunology More from this journal
- Volume:
- 6
- Issue:
- 59
- Article number:
- eabe5084
- Publication date:
- 2021-05-21
- Acceptance date:
- 2021-04-22
- DOI:
- EISSN:
-
2470-9468
- Language:
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English
- Keywords:
- Pubs id:
-
1174002
- Local pid:
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pubs:1174002
- Deposit date:
-
2021-04-30
- ARK identifier:
Terms of use
- Copyright holder:
- CS Hardman et al.
- Copyright date:
- 2021
- Rights statement:
- © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. https://www.sciencemag.org/about/science-licenses-journal-article-reuse This is an article distributed under the terms of the Science Journals Default License.
- Notes:
- This is the accepted manuscript version of the article. The final published version is available from the American Association for the Advancement of Science at https://doi.org/10.1126/sciimmunol.abe5084
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