The Journal of Experimental Medicine · 2017 · 161 citations · 41 references
Life SciencesCell BiologyImmunologyCellular ImmunologyImmunoregulationInflammationCell-mediated ImmunityCytokine BiologyDendritic Cell BiologyT Cell ActivationT Cell BiologyT Cell DifferentiationCd4 Positive T CellsDendritic Cell-t Cell InteractionNaive T CellsT Follicular Helper Cell DifferentiationT Follicular Helper CellsT-helper Cell PolarizationTh2 Immune ResponseTh2 Polarization
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. TSLP-activated 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.
41