Activin A programs the differentiation of human TFH cells.

TitleActivin A programs the differentiation of human TFH cells.
Publication TypeJournal Article
Year of Publication2016
AuthorsLocci M, Wu JE, Arumemi F, Mikulski Z, Dahlberg C, Miller AT, Crotty S
JournalNat Immunol
Date Published08/01/2016
ISSN1529-2916
Abstract

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.

DOI10.1038/ni.3494
Alternate JournalNat. Immunol.
PubMed ID27376469
Grant ListR01 AI072543 / AI / NIAID NIH HHS / United States
U19 AI096187 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
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