title: Activin A programs the differentiation of human TFH cells.
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.
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Michela
authors.initials: M
authors.lastname: Locci
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Wu
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Fortuna
authors.initials: F
authors.lastname: Arumemi
authors.affiliation: Microscopy Core Facility, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Mikulski
authors.affiliation: Genomics Institute of the Novartis Research Foundation, La Jolla, California, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Dahlberg
authors.affiliation: Genomics Institute of the Novartis Research Foundation, La Jolla, California, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Miller
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, 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.
authors.forename: Shane
authors.identifier: 0000-0002-6484-6262
authors.initials: S
authors.lastname: Crotty
mesh_terms: D028341:Activins / Q000378:metabolism*; D000818:Animals; D005075:Biological Evolution; D002454:Cell Differentiation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011323:Primates; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D013045:Species Specificity; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D051899:Smad2 Protein; D051900:Smad3 Protein; C422405:activin A; D028341:Activins