Expression of a BTB-ZF transcription factor controls the function of an innate-like Tregs essential for intestinal homeostasis

• Published in: The Journal of immunology (1950) 2022-05, Vol.208 (1_Supplement), p.113-113.24
• Main Authors: Krzyzanowska, Agata K, Haynes, Rashade A, Kovalovsky, Damian, Lin, Hsinching, Edelblum, Karen L, Corcoran, Lynn M, Rabson, Arnold B, Denzin, Lisa K, Sant’Angelo, Derek B
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.208.Supp.113.24

The BTB-ZF genes are a family of 49 transcription factors that control the lineage specification and development of key effector functions of different subsets of lymphocytes. Using a single-cell BTB-ZF transcription factor expression analysis, we identified a unique subset of T regulatory cells (Tregs). These Tregs are genetically and phenotypically distinct from the larger conventional Treg population. For instance, analogous to natural killer (NKT) cells they have an activated phenotype (CD62Llo, CD44hi) and constitutively express IL-10. Interestingly, these characteristics are acquired early during T cell development. The defining transcription factor is induced during thymic development, binds the IL-10 promoter, and enables T cells to rapidly produce the cytokine. The subset of Tregs is enriched in the intestine and expands during acute colitis. The deletion of the defining transcription factor in T cells results in intestinal epithelial layer damage causing loss of the barrier function making mice highly vulnerable to severe disease and death from induced colitis. Moreover, in the absence of the transcription factor in T cells, normal intestinal macrophage responses are disrupted most likely due to decreased production of IL-10 by the Tregs. Therefore, by profiling BTB-ZF transcription factor expression, we have identified a distinct subset of T cells with potent immunosuppressive abilities that are essential for the health of the intestine. Numerous aspects of these Tregs are parallel to NKT cells, indicating an existence of “naïve” Tregs that have innate-like effector functions acquired independently from the differentiation in the periphery. Supported by NIH/NIAID R01 AI122757-01 Careers in Immunology Fellowships – 2021