2024/12/27 by Muhammad Azeem, Moutaz Helal, Stefan Klein‐Hessling +4 · 1 voice
Immunology and Microbiology · #Immune Cell Function and Interaction #Immunotherapy and Immune Responses #T-cell and B-cell Immunology
paper · pdf · doi:10.1016/j.jid.2024.11.014
openalex publication_date 2024/12/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
A plethora of data supports a major role of CD4 + and CD8 + T lymphocytes for the initiation, progression, and maintenance of allergic contact dermatitis. However, in-depth understanding of the molecular mechanisms is still limited. NFATc1 plays an essential role in T-cell activation. We therefore investigated its impact on contact hypersensitivity, the mouse model for allergic contact dermatitis. The contact hypersensitivity response to 2,4,6-trinitrochlorobenzene was diminished in Nfatc1 fl/fl xCd4-cre mice ( Nfatc1 −/− ) compared with that in wild-type mice and associated with a lower percentage of IL-17–producing CD8 + T (Tc17) cells in both inflamed skin and draining lymph nodes. In vitro Tc17 polarization assays revealed that Nfatc1 −/− CD8 + T cells have a reduced capacity to polarize into Tc17 cells. Applying single-cell RNA sequencing, we realized that NFATc1 controls the T-cell differentiation fate. In the absence of NFATc1, CD8 + T cells favor the development of IFN-γ–secreting CD8 + T (Tc1) lymphocytes, whereas in its presence, they turn into Tc17 cells. Finally, the adoptive transfer of 2,4,6-trinitrochlorobenzene–sensitized wild-type CD8 + T cells restored the contact hypersensitivity response in naïve Nfatc1 −/− mice. Our data demonstrate that NFATc1 contributes to the development of Tc17 cells and might present a promising target to alleviate CD8 + T-cell–mediated allergic responses.