TY - JOUR
T1 - TSLP-activated dendritic cells induce human T follicular helper cell differentiation through OX40-ligand
AU - Pattarini, Lucia
AU - Trichot, Coline
AU - Bogiatzi, Sofia
AU - Grandclaudon, Maximilien
AU - Meller, Stephan
AU - Keuylian, Zela
AU - Durand, Melanie
AU - Volpe, Elisabetta
AU - Madonna, Stefania
AU - Cavani, Andrea
AU - Chiricozzi, Andrea
AU - Romanelli, Marco
AU - Hori, Toshiyuki
AU - Hovnanian, Alain
AU - Homey, Bernhard
AU - Soumelis, Vassili
PY - 2017/5/1
Y1 - 2017/5/1
N2 - T follicular helper cells (Tfh) are important regulators of humoral responses. Human Tfh polarization pathways have been thus far associated with Th1 and Th17 polarization pathways. How human Tfh cells differentiate in Th2-skewed environments is unknown. We show that thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs) promote human Tfh differentiation from naive CD4 T cells. We identified a novel population, distinct from Th2 cells, expressing IL-21 and TNF, suggestive of inflammatory cells. TSLP-induced T cells expressed CXCR5, CXCL13, ICOS, PD1, BCL6, BTLA, and SAP, among other Tfh markers. Functionally, TSLP-DC-polarized T cells induced IgE secretion by memory B cells, and this depended on IL-4Rα. TSLPactivated DCs stimulated circulating memory Tfh cells to produce IL-21 and CXCL13. Mechanistically, TSLP-induced Tfh differentiation depended on OX40-ligand, but not on ICOS-ligand. Our results delineate a pathway of human Tfh differentiation in Th2 environments.
AB - T follicular helper cells (Tfh) are important regulators of humoral responses. Human Tfh polarization pathways have been thus far associated with Th1 and Th17 polarization pathways. How human Tfh cells differentiate in Th2-skewed environments is unknown. We show that thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs) promote human Tfh differentiation from naive CD4 T cells. We identified a novel population, distinct from Th2 cells, expressing IL-21 and TNF, suggestive of inflammatory cells. TSLP-induced T cells expressed CXCR5, CXCL13, ICOS, PD1, BCL6, BTLA, and SAP, among other Tfh markers. Functionally, TSLP-DC-polarized T cells induced IgE secretion by memory B cells, and this depended on IL-4Rα. TSLPactivated DCs stimulated circulating memory Tfh cells to produce IL-21 and CXCL13. Mechanistically, TSLP-induced Tfh differentiation depended on OX40-ligand, but not on ICOS-ligand. Our results delineate a pathway of human Tfh differentiation in Th2 environments.
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U2 - 10.1084/jem.20150402
DO - 10.1084/jem.20150402
M3 - Article
C2 - 28428203
AN - SCOPUS:85021857198
VL - 214
SP - 1529
EP - 1546
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 5
ER -