CD100 boosts the inflammatory response in the challenge phase of allergic contact dermatitis in mice

Abstract

AbstractBackgroundAllergic contact dermatitis (ACD) is an inflammatory disease with a complex pathophysiology in which epidermal‐resident memory CD8+ T (TRM) cells play a key role. The mechanisms involved in the activation of CD8+ TRM cells during allergic flare‐up responses are not understood.MethodsThe expression of CD100 and its ligand Plexin B2 on CD8+ TRM cells and keratinocytes before and after allergen exposure was determined by flow cytometry and RT‐qPCR. The role of CD100 in the inflammatory response during the challenge phase of ACD was determined in a model of ACD in CD100 knockout and wild‐type mice.ResultsWe show that CD8+ TRM cells express CD100 during homeostatic conditions and up‐regulate it following re‐exposure of allergen‐experienced skin to the experimental contact allergen 1‐fluoro‐2,4‐dinitrobenzene (DNFB). Furthermore, Plexin B2 is up‐regulated on keratinocytes following exposure to some contact allergens. We show that loss of CD100 results in a reduced inflammatory response to DNFB with impaired production of IFNγ, IL‐17A, CXCL1, CXCL2, CXCL5, and IL‐1β and decreased recruitment of neutrophils to the epidermis.ConclusionOur study demonstrates that CD100 is expressed on CD8+ TRM cells and is required for full activation of CD8+ TRM cells and the flare‐up response of ACD.