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

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 p...

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Published inScience immunology Vol. 6; no. 59
Main Authors Hardman, Clare S, Chen, Yi-Ling, Salimi, Maryam, Nahler, Janina, Corridoni, Daniele, Jagielowicz, Marta, Fonseka, Chathuranga L, Johnson, David, Repapi, Emmanouela, Cousins, David J, Barlow, Jillian L, McKenzie, Andrew N J, Simmons, Alison, Ogg, Graham
Format Journal Article
LanguageEnglish
Published United States 21.05.2021
Subjects
Adult
Allergens - immunology
Antigens, Dermatophagoides - immunology
Cytokines - immunology
Humans
Immunity, Innate
Lymphocytes - immunology
Mutation
Nod2 Signaling Adaptor Protein - genetics
Nod2 Signaling Adaptor Protein - immunology
Skin - immunology
Skin - microbiology
Staphylococcal Infections - immunology
Staphylococcus aureus
Toll-Like Receptor 2 - immunology
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Summary: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 and 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 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 mutations. In addition, we show that signaling can stimulate autophagy in ILC2, which was also impaired in patients with 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.
ISSN:2470-9468
DOI:10.1126/sciimmunol.abe5084