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Nat Immunol. 2016 Aug;17(8):976-84. doi: 10.1038/ni.3494. Epub 2016 Jul 4.

Activin A programs the differentiation of human TFH cells.

Author information

Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
Microscopy Core Facility, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
Genomics Institute of the Novartis Research Foundation, La Jolla, California, USA.
Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California, USA.
Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, California, USA.


Follicular helper T cells (TFH cells) are CD4(+) T cells specialized in helping B cells and are associated both with protective antibody responses and autoimmune diseases. The promise of targeting TFH cells therapeutically has been limited by fragmentary understanding of extrinsic signals that regulate the differentiation of human TFH cells. A screen of a human protein library identified activin A as a potent regulator of TFH cell differentiation. Activin A orchestrated the expression of multiple genes associated with the TFH program, independently or in concert with additional signals. TFH cell programming by activin A was antagonized by the cytokine IL-2. Activin A's ability to drive TFH cell differentiation in vitro was conserved in non-human primates but not in mice. Finally, activin-A-induced TFH programming was dependent on signaling via SMAD2 and SMAD3 and was blocked by pharmacological inhibitors.

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