IL-6 effector function of group 2 innate lymphoid cells (ILC2) is NOD2 dependent
| Autor: | Yi-Ling Chen, David Johnson, Clare S. Hardman, Jillian L. Barlow, C. L. Fonseka, Janina Nahler, Alison Simmons, Maryam Salimi, Marta Jagielowicz, Andrew N. J. McKenzie, Emmanouela Repapi, David J. Cousins, Graham S. Ogg, Daniele Corridoni |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Staphylococcus aureus medicine.medical_treatment Immunology Nod2 Signaling Adaptor Protein Human skin Biology Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine NOD2 medicine Humans Antigens Dermatophagoides Lymphocytes Receptor Skin Effector Innate lymphoid cell General Medicine Allergens Staphylococcal Infections Immunity Innate Toll-Like Receptor 2 TLR2 030104 developmental biology Cytokine chemistry 030220 oncology & carcinogenesis Mutation Cytokines Muramyl dipeptide |
| Zdroj: | Sci Immunol |
| ISSN: | 2470-9468 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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