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Interleukin-2-induced skin inflammation
Charline Sommer1, Jarish N Cohen2,3, Susann Dehmel1
1Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Member of the Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Hannover, Germany.
Interleukin-2 (IL-2) therapy can cause skin rashes due to immune reactions in the skin. Innate lymphoid cells and CD25 on regulatory T cells are key players in these IL-2-induced side effects.
Area of Science:
- Immunology
- Dermatology
- Pharmacology
Background:
- Recombinant human interleukin-2 (IL-2) is a therapeutic for cancer and inflammatory diseases.
- Skin rashes are a common side effect limiting IL-2 therapy.
- Understanding the cellular and molecular mechanisms of IL-2-induced skin inflammation is crucial.
Purpose of the Study:
- To identify key cells and molecules involved in IL-2-induced cutaneous immune reactions.
- To investigate the role of CD25 (IL-2 receptor α) in IL-2-mediated skin inflammation.
- To elucidate the function of CD25 on skin regulatory T cells (Tregs) in modulating IL-2 side effects.
Main Methods:
- Intradermal injection of IL-2 into wild-type (WT) mice.
- Characterization of immune cell subsets in the skin.
- Topical genetic deletion of CD25 on cutaneous cells and skin Tregs.
- Analysis of IL-4, IL-13, and IL-17 production.
Main Results:
- IL-2 injection increased IL-4/IL-13-producing group 2 innate lymphoid cells and IL-17-producing dermal γδ T cells in the skin.
- This resulted in a shift towards type 2 and type 17 immune responses.
- Genetic reduction of CD25 on skin cells decreased IL-2-dependent inflammation.
- Selective reduction of CD25 on skin Tregs exacerbated IL-2-induced immune cell infiltration.
Conclusions:
- Innate lymphoid immune cells are critical mediators of IL-2 therapy-induced skin side effects.
- CD25 plays a significant role in mediating IL-2-induced skin inflammation.
- CD25 on skin Tregs is essential for suppressing IL-2-induced cutaneous inflammation.
