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Thymic stromal lymphopoietin-activated plasmacytoid dendritic cells induce the generation of FOXP3+ regulatory T cells in human thymus.
J Immunol. 2010 Mar 15; 184(6):2999-3007.JI

Abstract

Human thymus contains major dendritic cell (DC) subsets, myeloid DCs (mDCs), and plasmacytoid DCs (pDCs). We previously showed that mDCs, educated by thymic stromal lymphopoietin (TSLP) produced by the epithelial cells of the Hassall's corpuscles, induced differentiation of CD4(+)CD25(-) thymocytes into Forkhead Box P3(+) (FOXP3(+)) regulatory T cells (T(R)) within the medulla of human thymus. In this study, we show that pDCs expressed the TSLP receptor and IL-7 receptor alpha complexes upon activation and became responsive to TSLP. TSLP-activated human pDCs secrete macrophage-derived chemokine CCL-22 and thymus- and activation-regulated chemokine CCL-17 but not Th1- or Th2-polarizing cytokines. TSLP-activated pDCs induced the generation of FOXP3(+) T(R) from CD4(+)CD8(-)CD25(-) thymocytes, which could be strongly inhibited by Th1-polarizing cytokine IL-12 or Th2-polarizing cytokine IL-4. Interestingly, the FOXP3(+) T(R) induced by the TSLP-pDCs expressed more IL-10 but less TGF-beta than that induced by the TSLP-mDCs. These data suggest that TSLP expressed by thymic epithelial cells can activate mDCs and pDCs to positively select the FOXP3(+) T(R) with different cytokine production potential in human thymus. The inability of TSLP to induce DC maturation without producing Th1- or Th2-polarizing cytokines may provide a thymic niche for T(R) development.

Links

Publisher Full Text
ncbi.nlm.nih.gov
jimmunol.org
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Authors+Show Affiliations

Hanabuchi S
Department of Immunology and Center for Cancer Immunology Research, University of Texas MD Anderson Cancer Center, Houston, TX 77030-1903, USA.
Ito T
No affiliation info available
Park WR
No affiliation info available
Watanabe N
No affiliation info available
Shaw JL
No affiliation info available
Roman E
No affiliation info available
Arima K
No affiliation info available
Wang YH
No affiliation info available
Voo KS
No affiliation info available
Cao W
No affiliation info available
Liu YJ
No affiliation info available

MeSH

AdultB7-1 AntigenB7-2 AntigenCell DifferentiationCells, CulturedChemokine CCL17Chemokine CCL22Child, PreschoolCoculture TechniquesCytokinesDendritic CellsForkhead Transcription FactorsHumansInfantInfant, NewbornInterleukin-7 Receptor alpha SubunitReceptors, CytokineStromal CellsT-Lymphocytes, RegulatoryTh1 CellsTh2 CellsThymus Gland

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20173030

Citation

Hanabuchi, Shino, et al. "Thymic Stromal Lymphopoietin-activated Plasmacytoid Dendritic Cells Induce the Generation of FOXP3+ Regulatory T Cells in Human Thymus." Journal of Immunology (Baltimore, Md. : 1950), vol. 184, no. 6, 2010, pp. 2999-3007.
Hanabuchi S, Ito T, Park WR, et al. Thymic stromal lymphopoietin-activated plasmacytoid dendritic cells induce the generation of FOXP3+ regulatory T cells in human thymus. J Immunol. 2010;184(6):2999-3007.
Hanabuchi, S., Ito, T., Park, W. R., Watanabe, N., Shaw, J. L., Roman, E., Arima, K., Wang, Y. H., Voo, K. S., Cao, W., & Liu, Y. J. (2010). Thymic stromal lymphopoietin-activated plasmacytoid dendritic cells induce the generation of FOXP3+ regulatory T cells in human thymus. Journal of Immunology (Baltimore, Md. : 1950), 184(6), 2999-3007. https://doi.org/10.4049/jimmunol.0804106
Hanabuchi S, et al. Thymic Stromal Lymphopoietin-activated Plasmacytoid Dendritic Cells Induce the Generation of FOXP3+ Regulatory T Cells in Human Thymus. J Immunol. 2010 Mar 15;184(6):2999-3007. PubMed PMID: 20173030.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thymic stromal lymphopoietin-activated plasmacytoid dendritic cells induce the generation of FOXP3+ regulatory T cells in human thymus. AU - Hanabuchi,Shino, AU - Ito,Tomoki, AU - Park,Woon-Ryon, AU - Watanabe,Norihiko, AU - Shaw,Joanne L, AU - Roman,Eulogia, AU - Arima,Kazuhiko, AU - Wang,Yui-Hsi, AU - Voo,Kui Shin, AU - Cao,Wei, AU - Liu,Yong-Jun, Y1 - 2010/02/19/ PY - 2010/2/23/entrez PY - 2010/2/23/pubmed PY - 2010/5/4/medline SP - 2999 EP - 3007 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 184 IS - 6 N2 - Human thymus contains major dendritic cell (DC) subsets, myeloid DCs (mDCs), and plasmacytoid DCs (pDCs). We previously showed that mDCs, educated by thymic stromal lymphopoietin (TSLP) produced by the epithelial cells of the Hassall's corpuscles, induced differentiation of CD4(+)CD25(-) thymocytes into Forkhead Box P3(+) (FOXP3(+)) regulatory T cells (T(R)) within the medulla of human thymus. In this study, we show that pDCs expressed the TSLP receptor and IL-7 receptor alpha complexes upon activation and became responsive to TSLP. TSLP-activated human pDCs secrete macrophage-derived chemokine CCL-22 and thymus- and activation-regulated chemokine CCL-17 but not Th1- or Th2-polarizing cytokines. TSLP-activated pDCs induced the generation of FOXP3(+) T(R) from CD4(+)CD8(-)CD25(-) thymocytes, which could be strongly inhibited by Th1-polarizing cytokine IL-12 or Th2-polarizing cytokine IL-4. Interestingly, the FOXP3(+) T(R) induced by the TSLP-pDCs expressed more IL-10 but less TGF-beta than that induced by the TSLP-mDCs. These data suggest that TSLP expressed by thymic epithelial cells can activate mDCs and pDCs to positively select the FOXP3(+) T(R) with different cytokine production potential in human thymus. The inability of TSLP to induce DC maturation without producing Th1- or Th2-polarizing cytokines may provide a thymic niche for T(R) development. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/20173030/Thymic_stromal_lymphopoietin_activated_plasmacytoid_dendritic_cells_induce_the_generation_of_FOXP3+_regulatory_T_cells_in_human_thymus_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=20173030 DB - PRIME DP - Unbound Medicine ER -