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RNAseq analysis for tails, and ears from Ikbkb mut/mut and Ikbkb wt/wt mice

ABSTRACT: Loss-of-function mutations have provided crucial insights into the immunoregulatory actions of Foxp3+ regulatory T cells (Tregs). By contrast, we know very little about the consequences of defects that amplify aspects of Treg function or differentiation. We report that mice heterozygous for an Ikbkb gain-of-function (GoF) mutation develop psoriasis. Doubling the gene dose (IkbkbGoF/GoF) results in dactylitis, spondylitis, and characteristic nail changes, which are features of psoriatic arthritis. IkbkbGoF mice exhibit a selective expansion of Foxp3+ CD25+ Tregs of which a subset express IL-17. These modified Tregs were enriched at the inflamed tissues and spleen, and their transfer was sufficient to induce disease without conventional T cells. Single-cell transcriptional and phenotyping analyses of isolated Tregs revealed expansion of non-lymphoid tissue (tissue-resident) Tregs expressing Th17-related genes, Helios, tissue-resident markers including CD103 and CD69, and a prominent NF-kB transcriptome. Thus, IKK2 regulates tissue-resident Treg differentiation, and overactivity drives dose-dependent skin and systemic inflammation.

ORGANISM(S): Mus musculus

PROVIDER: GSE248917 | GEO | 2024/01/09

REPOSITORIES: GEO

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