Lack of Type 2 Innate Lymphoid Cells Promotes a Type I-Driven Enhanced Immune Response in Contact Hypersensitivity

David A Rafei-Shamsabadi,Saskia Van De Poel,Britta Dorn,Stefanie Kunz,Stefan F Martin,Christoph S.N Klose,Sebastian J Arnold,Yakup Tanriver,Karolina Ebert,Andreas Diefenbach,Timotheus Y.F Halim,Andrew N.J Mckenzie,Thilo Jakob

doi:10.1016/j.jid.2018.03.001

David A Rafei-Shamsabadi, Saskia Van De Poel + Show 11 more

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https://doi.org/10.1016/j.jid.2018.03.001

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Allergic contact dermatitis and its animal model, contact hypersensitivity, are T-cell-mediated inflammatory skin diseases that require activation of the innate immune system. Here we investigate the role of innate lymphoid cells (ILCs) during the elicitation phase of 2,4,6-trinitrochlorobenzene-induced contact hypersensitivity using EomesGfp/+ x Rorc(γt)-CreTg x Rosa26RYfp/+ reporter mice. Ear swelling responses, cutaneous ILC numbers, and cytokine production were determined at different time points. Functional analyses were performed in a CD90.1/.2 congenic adoptive transfer model that allowed selective antibody-mediated depletion of ILCs before hapten challenge, and in Rorasg/floxIl7rCre/+ mice, which lack ILC2. Hapten challenge induced early increases of natural killer cells in skin and ear draining lymph nodes corresponding to the peak ear swelling response. In contrast, ILC1, 2, and 3 showed a delayed increase in numbers corresponding to the contact hypersensitivity resolution phase. Hapten challenge induced increased marker cytokines in all ILC subtypes and an activated phenotype in ILC2. Depletion of all ILC resulted in a significantly enhanced ear swelling response. Similarly, ILC2-deficient mice (Rorasg/floxIl7rCre/+) displayed increased ear swelling responses on hapten challenge, suggesting that ILC2 act as negative regulators in the type 1-dominated immune response of contact hypersensitivity.

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ILC2 represent the predominant innate lymphoid cell (ILC) subset in the skin followed by ILC3 and by far fewer ILC1 and natural killer (NK)
We conclude that ILC2 and ILC3 represent the dominant resident innate lymphoid cell populations under steady-state conditions in the skin
On hapten challenge NK cells increase in ear skin before

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Allergy Research Group, Department of Dermatology, Medical CenterUniversity of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; 2Experimental Dermatology and Allergy Research. Center Giessen and Marburg, Campus Giessen, Justus Liebig University, Giessen, Germany; 3Institute of Medical Microbiology and Hygiene, University Medical Center, Freiburg, Germany; 4Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany; 5Department of Microbiology, Charité-University Medical Centre Berlin, Berlin, Germany; and 6Medical. Research Council, Laboratory of Molecular Biology, Cambridge, Cambridgeshire, UK. Current address: Jill Roberts Institute for Research in IBD, Weill Cornell. Current address: University of Cambridge, Cancer Research UKCambridge Institute, Robinson Way, Cambridge CB2 0RE, UK. Current address: Institute of Medical Virology, University Medical Center.

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