0000000000060125
AUTHOR
Lena Dietz
Nfatc1/Αa and Blimp-1 Support the Follicular and Effector Phenotype of Tregs
CD4 + CXCR5 + Foxp3 + T follicular regulatory (T FR ) cells control the germinal center responses. Like follicular helper T-cells, they express high levels of N uclear F actor of A ctivated T -cells c1 , predominantly its short isoform NFATc1/αA. Ablation of NFATc1 in Tregs prevents upregulation of CXCR5 and migration of T FR cells into B-cell follicles. By contrast, constitutive active NFATc1/αA defines the surface density of CXCR5, whose level determines how deep a T FR migrates into the GC and how effectively it controls antibody production. NFATc1/αA is necessary to overcome T FR -expressed B l ymphocyte- i nduced m aturation p rotein (Blimp-1), which can directly repress Cxcr5. Blimp-1…
NFAT1 deficit and NFAT2 deficit attenuate EAE via different mechanisms
EAE serves as an animal model for multiple sclerosis and is initiated by autoreactive T cells that infiltrate the CNS. Recognition of myelin-associated Ags within the CNS leads to activation of the transcription factor family NFAT. Here, we demonstrate an essential role for NFAT in disease induction, as the combined lack of NFAT1 (NFATc2) and NFAT2 (NFATc1) completely protected mice. Single deficiency of either NFAT1 or NFAT2 ameliorated the course of EAE, and NFAT2 ablation resulted in an obstructed proinflammatory reaction. However, NFAT1 deficit led to an anti-inflammatory response with nonpathogenic Th17 and Th2 cells concurrently secreting IL-17, IL-4, and IL-10. Both IL-4 and IL-10 co…
Lack of NFATc1 SUMOylation prevents autoimmunity and alloreactivity
A novel transgenic mouse, in which the transcription factor NFATc1 bears lysine-to-arginine mutations that prevent modification by SUMO, develops normally and is healthy. However, SUMO-insensitive NFATc1 transmits strong tolerogenic signals, thus preventing autoimmune and alloimmune T cell responses.