NFATc1 fosters allergic contact dermatitis responses by enhancing the induction of IL-17-producing CD8 cells.

A plethora of data supports a major role of CD4 and CD8 T lymphocytes for the initiation, progression and maintenance of allergic contact dermatitis (ACD). However, in-depth understanding of the molecular mechanisms is still limited. NFATc1 plays an essential role in T cell activation.

NFATc1 induction by an intronic enhancer restricts NKT γδ cell formation.

In thymus, the ablation of T cell receptor (TCR)-activated transcription factor NFATc1 or its inducible isoforms during the double-negative (DN) stages of thymocyte development leads to a marked increase in γδ thymocytes whereas the development of αβ thymocytes remains mostly unaffected. These γδ thymocytes are characterized by the upregulation of the promyelocytic leukemia zinc-finger factor (PLZF), the "master regulator" of natural killer T (NKT) cell development, and the acquisition of an NKT γδ cell phenotype with higher cell survival rates. The suppressive function of NFATc1 in NKT γδ cell formation critically depends on the remote enhancer E2, which is essential for the inducible expression of NFATc1 directed by its distal promoter P1.

Hematopoietic Stem and Progenitor Cell Maintenance and Multiple Lineage Differentiation Is an Integral Function of NFATc1.

Hematopoietic stem and progenitor cell (HSPC) maintenance and the differentiation of various lineages is a highly complex but precisely regulated process. Multiple signaling pathways and an array of transcription factors influence HSPC maintenance and the differentiation of individual lineages to constitute a functional hematopoietic system. Nuclear factor of activated T cell (NFAT) family transcription factors have been studied in the context of development and function of multiple mature hematopoietic lineage cells.

NFATc1/αA and Blimp-1 Support the Follicular and Effector Phenotype of Tregs.

CD4CXCR5Foxp3 T-follicular regulatory (T) cells control the germinal center responses. Like T-follicular helper cells, they express high levels of , predominantly its short isoform NFATc1/αA. Ablation of NFATc1 in Tregs prevents upregulation of CXCR5 and migration of T cells into B-cell follicles.