Find in Library
Search millions of books, articles, and more
Indexed Open Access Databases
NFATc1/αA and Blimp-1 Support the Follicular and Effector Phenotype of Tregs
oleh: Anika Koenig, Martin Vaeth, Yin Xiao, Cristina M. Chiarolla, Raghu Erapaneedi, Matthias Klein, Lena Dietz, Nadine Hundhausen, Snigdha Majumder, Felix Schuessler, Tobias Bopp, Tobias Bopp, Tobias Bopp, Tobias Bopp, Stefan Klein-Hessling, Andreas Rosenwald, Andreas Rosenwald, Ingolf Berberich, Friederike Berberich-Siebelt
Format: | Article |
---|---|
Diterbitkan: | Frontiers Media S.A. 2022-01-01 |
Deskripsi
CD4+CXCR5+Foxp3+ T-follicular regulatory (TFR) cells control the germinal center responses. Like T-follicular helper cells, they express high levels of Nuclear Factor of Activated T-cells c1, predominantly its short isoform NFATc1/αA. Ablation of NFATc1 in Tregs prevents upregulation of CXCR5 and migration of TFR cells into B-cell follicles. By contrast, constitutive active NFATc1/αA defines the surface density of CXCR5, whose level determines how deep a TFR migrates into the GC and how effectively it controls antibody production. As one type of effector Treg, TFR cells express B lymphocyte-induced maturation protein-1 (Blimp-1). Blimp-1 can directly repress Cxcr5 and NFATc1/αA is necessary to overcome this Blimp-1-mediated repression. Interestingly, Blimp-1 even reinforces the recruitment of NFATc1 to Cxcr5 by protein-protein interaction and by those means cooperates with NFATc1 for Cxcr5 transactivation. On the contrary, Blimp-1 is necessary to counterbalance NFATc1/αA and preserve the Treg identity. This is because although NFATc1/αA strengthens the follicular development of Tregs, it bears the inherent risk of causing an ex-Treg phenotype.