Murine thymic stromal lymphopoietin promotes the differentiation of regulatory T cells from thymic CD4(+)CD8(-)CD25(-) naïve cells in a dendritic cell-independent manner.
Human thymic stromal lymphopoietin (TSLP) activates dendritic cells (DCs), which promote the proliferation and differentiation of CD4+ T cells. However, murine TSLP (mTSLP) can act directly on CD4+ T cells and bring about their differentiation. We studied the role of mTSLP in the generation of CD4+CD25+FoxP3+ T cells from thymocytes. mTSLP promoted the differentiation of CD4+ single-positive thymocytes into CD4+CD25+FoxP3+ T cells. Although we cannot exclude an effect of TSLP mediated through DCs due to co-stimulatory effects, mTSLP appears to act directly on thymocytes. T-cell receptor and TSLP receptor signaling act synergistically on thymocytes to generate CD4+CD25+FoxP3+ T cells. mTSLP may play an important role in maintaining immune tolerance by promoting the conversion of thymocytes into natural regulatory T cells via escape from negative selection.
Lee
June-Yong
JY
The Rheumatism Research Center, Catholic Research Institutes of Medical Sciences, The Catholic University of Korea, Seoul, Korea.
Lim
Yu-Mi
YM
Park
Min-Jung
MJ
Min
So-Youn
SY
Cho
Mi-La
ML
Sung
Young-Chul
YC
Park
Se-Ho
SH
Kim
Ho-Youn
HY
Cho
Young-Gyu
YG
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse