Interleukin‐2‐induced skin inflammation

Abstract

Recombinant human IL‐2 has been used to treat inflammatory diseases and cancer; however, side effects like skin rashes limit the use of this therapeutic. To identify key molecules and cells inducing this side effect, we characterized IL‐2‐induced cutaneous immune reactions and investigated the relevance of CD25 (IL‐2 receptor α) in the process. We injected IL‐2 intradermally into WT mice and observed increases in immune cell subsets in the skin with preferential increases in frequencies of IL‐4‐ and IL‐13‐producing group 2 innate lymphoid cells and IL‐17‐producing dermal γδ T cells. This overall led to a shift toward type 2/type 17 immune responses. In addition, using a novel topical genetic deletion approach, we reduced CD25 on skin, specifically on all cutaneous cells, and found that IL‐2‐dependent effects were reduced, hinting that CD25 — at least partly — induces this skin inflammation. Reduction of CD25 specifically on skin Tregs further augmented IL‐2‐induced immune cell infiltration, hinting that CD25 on skin Tregs is crucial to restrain IL‐2‐induced inflammation. Overall, our data support that innate lymphoid immune cells are key cells inducing side effects during IL‐2 therapy and underline the significance of CD25 in this process.