Thymic Stromal Lymphopoietin-Activated Plasmacytoid Dendritic Cells Induce the Generation of FOXP3+ Regulatory T Cells in Human Thymus

被引:155
作者
Hanabuchi, Shino [2 ]
Lto, Tomoki [4 ]
Park, Woon-Ryon [2 ]
Watanabe, Norihiko [5 ]
Shaw, Joanne L. [2 ]
Roman, Eulogia [3 ]
Arima, Kazuhiko [2 ]
Wang, Yui-Hsi [6 ]
Voo, Kui Shin [2 ]
Cao, Wei [2 ]
Liu, Yong-Jun [1 ,2 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Unit 901, Houston, TX 77030 USA
[2] Univ Texas MD Anderson Canc Ctr, Ctr Canc Immunol Res, Houston, TX 77030 USA
[3] Univ Texas Houston, Hlth Sci Ctr, Dept Pathol & Lab Med, Houston, TX 77030 USA
[4] Kansai Med Univ, Dept Internal Med 1, Osaka, Japan
[5] Kyoto Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Kyoto, Japan
[6] Univ Cincinnati, Cincinnati Childrens Hosp, Med Ctr, Div Allergy & Immunol, Cincinnati, OH 45229 USA
基金
美国国家卫生研究院;
关键词
MACROPHAGE-DERIVED CHEMOKINE; MEDULLARY EPITHELIAL-CELLS; CORTICAL EPITHELIUM; SELF; TOLERANCE; CD4(+); SELECTION; EXPRESSION; DIFFERENTIATION; COSTIMULATION;
D O I
10.4049/jimmunol.0804106
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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+ TR 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. The Journal of Immunology, 2010, 184: 2999-3007.
引用
收藏
页码:2999 / 3007
页数:9
相关论文
共 41 条
  • [1] Macrophage-derived chemokine and EBI1-ligand chemokine attract human thymocytes in different stage of development and are produced by distinct subsets of medullary epithelial cells: Possible implications for negative selection
    Annunziato, F
    Romagnani, P
    Cosmi, L
    Beltrame, C
    Steiner, BH
    Lazzeri, E
    Raport, CJ
    Galli, G
    Manetti, R
    Mavilia, C
    Vanini, V
    Chantry, D
    Maggi, E
    Romagnani, S
    [J]. JOURNAL OF IMMUNOLOGY, 2000, 165 (01) : 238 - 246
  • [2] Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells
    Aschenbrenner, Katharina
    D'Cruz, Louise M.
    Vollmann, Elisabeth H.
    Hinterberger, Maria
    Emmerich, Jan
    Swee, Lee Kim
    Rolink, Antonius
    Klein, Ludger
    [J]. NATURE IMMUNOLOGY, 2007, 8 (04) : 351 - 358
  • [3] Human thymus contains IFN-α-producing CD11c-, myeloid CD11c+ and mature interdigitating dendritic cells
    Bendriss-Vermare, N
    Barthélémy, C
    Durand, I
    Bruand, C
    Dezutter-Dambuyant, C
    Moulian, N
    Berrih-Aknin, S
    Caux, C
    Trinchieri, G
    Brière, F
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (07) : 835 - 844
  • [4] Major histocompatibility complex class II-positive cortical epithelium mediates the selection of CD4+25+ immunoregulatory T cells
    Bensinger, SJ
    Bandeira, A
    Jordan, MS
    Caton, AJ
    Laufer, TM
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 194 (04) : 427 - 438
  • [5] Beschorner WE, 1995, TRANSPLANTATION, V60, P1326
  • [6] Campbell JJ, 1999, J IMMUNOL, V163, P2353
  • [7] Chantry D, 1999, BLOOD, V94, P1890
  • [8] Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3
    Chen, WJ
    Jin, WW
    Hardegen, N
    Lei, KJ
    Li, L
    Marinos, N
    McGrady, G
    Wahl, SM
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (12) : 1875 - 1886
  • [9] Two developmentally distinct populations of dendritic cells inhabit the adult mouse thymus: Demonstration by differential importation of hematogenous precursors under steady state conditions
    Donskoy, E
    Goldschneider, I
    [J]. JOURNAL OF IMMUNOLOGY, 2003, 170 (07) : 3514 - 3521
  • [10] FONTAINEPERUS JC, 1981, J IMMUNOL, V126, P2310