T cell-intrinsic expression of HIC1 links retinoic acid to tissue residency

• DOI: 10.4049/jimmunol.204.supp.155.3
• Publication Date: 2023-01-01T14:09:13Z
• Authors: Michael Bramhall; Grace Rodrigues; Susan Christo; Laura Mackay; Colby Zaph
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

Abstract The interaction between micronutrients and the immune system is emerging as a key control point in cell function homeostasis disease. For example, vitamin A metabolite all-trans retinoic acid (atRA) has established roles migration effector function. Vitamin deficiency results significant reduction intestinal cells, which thought to be associated with lack of homing receptor expression reduced intestine. However, precise molecular pathways controlling remains unclear. Here, we show that atRA-inducible BTB-POZ transcriptional repressor Hypermethylated cancer 1 (HIC1, ZBTB29) controls T residency. Mice cell-intrinsic deletion HIC1 (Hic1ΔT mice) have numbers CD69+ CD103+ tissue resident memory (TRM) cells intestine, demonstrating atRA/HIC1 axis critical for establishing maintaining TRM cells. Further, following influenza virus infection, lungs are significantly Hic1ΔT mice, well mice treated pan-retinoic inhibitor BMS493, or cell-specific RARa (RaraΔT mice). Consistent this, activation naive CD8+ from humans presence IL-2, IL-15, TGFβ atRA generation ‘TRM-like’ share profile bona fide Taken together, these identify regulator residency, acting by inducing promoting residency gene program.