TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand.
We recently showed that dendritic cells (DCs) activated by thymic stromal lymphopoietin (TSLP) prime naive CD4(+) T cells to differentiate into T helper type 2 (Th2) cells that produced high amounts of tumor necrosis factor-alpha (TNF-alpha), but no interleukin (IL)-10. Here we report that TSLP induced human DCs to express OX40 ligand (OX40L) but not IL-12. TSLP-induced OX40L on DCs was required for triggering naive CD4(+) T cells to produce IL-4, -5, and -13. We further revealed the following three novel functional properties of OX40L: (a) OX40L selectively promoted TNF-alpha, but inhibited IL-10 production in developing Th2 cells; (b) OX40L lost the ability to polarize Th2 cells in the presence of IL-12; and (c) OX40L exacerbated IL-12-induced Th1 cell inflammation by promoting TNF-alpha, while inhibiting IL-10. We conclude that OX40L on TSLP-activated DCs triggers Th2 cell polarization in the absence of IL-12, and propose that OX40L can switch IL-10-producing regulatory Th cell responses into TNF-alpha-producing inflammatory Th cell responses.
Ito
Tomoki
T
Center for Cancer Immunology Research, Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, 77030, USA.
Wang
Yui-Hsi
YH
Duramad
Omar
O
Hori
Toshiyuki
T
Delespesse
Guy J
GJ
Watanabe
Norihiko
N
Qin
F Xiao-Feng
FX
Yao
Zhengbin
Z
Cao
Wei
W
Liu
Yong-Jun
YJ
D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000502:physiology*; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000502:physiology; D008213:Lymphocyte Activation / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D053278:OX40 Ligand; D051257:Proto-Oncogene Proteins c-maf / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000502:physiology*; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D050990:GATA3 Transcription Factor; D018836:Inflammation Mediators; D018793:Interleukin-13; C495607:MAF protein, human; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D051257:Proto-Oncogene Proteins c-maf; D011994:Recombinant Proteins; C089251:TNFSF4 protein, human; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D000094632:Thymic Stromal Lymphopoietin