Abstract
The role of innate lymphoid cells (ILC) in allergic contact dermatitis has not adequately been addressed. We investigated quantitative changes and functional relevance of ILCs during the elicitation phase of hapten-induced contact hypersensitivity (CHS). EomesGfp/+ x Rorc(γt)-CreTg x Rosa26RYfp/+ reporter mice were sensitized and challenged with the hapten TNCB. Ear swelling, ILC numbers and cytokine production were measured at different time points. For functional analysis we depleted ILCs in Rag1-/- mice before recieving sorted T-cells from sensitized donor mice (CD90.1) using either a CD90.2-specific or isotype mAb. In addition CHS was performed in Rorα+/floxIl7rCre mice, which selectively lack ILC2. The quantitative analysis of total cell numbers revealed early increases of natural killer (NK) cells in skin and skin draining lymph nodes 24h after allergen challenge, corresponding to the highest ear swelling response and leukocyte infiltrate in the skin. These cells produced high amounts of the type 1 cytokines IFNγ and TNFα. ILC1, 2 and 3 showed a delayed increase in total numbers starting from 48h after allergen challenge. ILC2 cells displayed an activated phenotype reflected by increased ICOS expression. Total ILC depletion through CD90.2 mAb administration resulted in a significantly enhanced ear swelling response. Finally, Rorα+/floxIl7rCre mice also displayed increased ear swelling responses after allergen challenge. In conclusion, our data support the concept of NK cells as main innate proinflammatory player and suggests that simultaneously activated ILC2 act as counter regulators in the type 1 dominated immune response of CHS.
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