TGF-β Is Required To Maintain the Pool of Immature Langerhans Cells in the Epidermis

被引:123
|
作者
Kel, Junda M. [1 ]
Girard-Madoux, Mathilde J. H. [1 ,2 ]
Reizis, Boris [3 ]
Clausen, Bjorn E. [1 ]
机构
[1] Erasmus MC, Univ Med Ctr, Dept Immunol, NL-3015 GE Rotterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands
[3] Columbia Univ, Med Ctr, Dept Microbiol & Immunol, New York, NY 10032 USA
来源
JOURNAL OF IMMUNOLOGY | 2010年 / 185卷 / 06期
关键词
DERMAL DENDRITIC CELLS; STEADY-STATE; IN-VIVO; CONTACT HYPERSENSITIVITY; T-CELLS; DEFICIENT MICE; LYMPH-NODES; E-CADHERIN; SKIN; ACTIVATION;
D O I
10.4049/jimmunol.1000981
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The pivotal role of TGF-beta in Langerhans cell (LC) development has been previously established in TGF-beta-deficient mice, which lack epidermal LCs. As to whether TGF-beta also governs LC homeostasis and function remains elusive. To assess the role of TGF-beta-mediated control of cutaneous dendritic cells (DCs) in vivo, we generated mice with a conditional knockout of the TGF-beta receptor 1 (T beta R1) under a DC-specific promoter (DC-T beta R1(del) mice). While initial LC seeding occurred in DC-T beta R1(del) mice, the cells disappeared from the epidermis during the first week of life. T beta R1-deficient LCs demonstrated spontaneous maturation and gained migratory potential based on increased surface expression of MHC class II, costimulatory molecules, and CCR7 and downregulation of E-cadherin. In parallel to their early loss from the epidermis, migrating LCs were reduced in the dermis and skin-draining lymph nodes of adult DC-T beta R1(del) mice, whereas the number of Langerin(+) dermal DCs was similar to wild-type. In the absence of LCs, low-dose contact hypersensitivity in DC-T beta R1(del) mice was significantly diminished. In contrast, ear swelling was restored to wild-type levels when a higher hapten dose was applied to efficiently target T beta R1-deficient dermal DCs. In conclusion, TGF-beta inhibits in vivo LC maturation and migratory phenotype, identifying TGF-beta as a critical factor controlling LC homeostasis in the steady state. The Journal of Immunology, 2010, 185: 3248-3255.
引用
收藏
页码:3248 / 3255
页数:8
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