Research ArticleINNATE IMMUNITY

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

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

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Skin sentinels

Group 2 innate lymphoid cells (ILC2) are the predominant ILC subset in the skin and are positioned to respond to barrier disruption. Hardman et al. examined the ability of ILC2 to directly sense skin pathogens. ILC2 from in vivo–challenged skin or peripheral blood showed an increase in NOD2 and TLR2 expression. ILC2 stimulated with a TLR2 agonist up-regulated IL-5 and IL-13 expression, but stimulation with both TLR2 agonist and Staphylococcus aureus muramyl dipeptide also induced IL-6 expression. Exposure of ILC2 to heat-killed skin-resident bacteria induced IL-6 expression, which was reduced by NOD2 pathway inhibition, and NOD2 signaling stimulated autophagy in ILC2. These findings define a role for ILC2 NOD2 in cutaneous bacterial sensing and regulation of IL-6 expression.

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