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CCCTC-binding factor controls the homeostatic maintenance and migration of Langerhans cells

 Tae-Gyun Kim  ;  Mikyoung Kim  ;  Jong-Joo Lee  ;  Sung Hee Kim  ;  Jeong Hwan Je  ;  Yangsin Lee  ;  Min-Ji Song  ;  Yeeun Choi  ;  Youn Wook Chung  ;  Chae Gyu Park  ;  Jin Won Cho  ;  Min-Geol Lee  ;  Yeon-Su Lee  ;  Hyoung-Pyo Kim 
 Journal of Allergy and Clinical Immunology, Vol.136(3) : 713-724, 2015 
Journal Title
 Journal of Allergy and Clinical Immunology 
Issue Date
BACKGROUND: Langerhans cells (LCs) are skin-resident dendritic cells (DCs) that orchestrate skin immunity. CCCTC-binding factor (CTCF) is a highly conserved DNA-binding protein that regulates higher-order chromatin organization and is involved in various gene regulation processes. OBJECTIVE: We sought to clarify a possible role for CTCF in LC homeostasis and function in vivo. METHODS: We used a conditional gene deletion mouse system to generate DC- and LC-specific CTCF-ablated mice. Short hairpin RNA-mediated RNA interference was used to silence CTCF expression in human monocyte-derived Langerhans cells. DC populations were assessed by using flow cytometry and immunofluorescence. Gene expression arrays were performed to identify genes regulated by CTCF in LCs. Contact hypersensitivity and epicutaneous sensitization responses were measured to examine the functional significance of CTCF ablation. RESULTS: DC-specific CTCF deletion led to a reduced pool of systemic DCs, with LCs most severely affected. Decreases in epidermal LC numbers were specifically associated with self-turnover defects. Interestingly, CTCF-deficient LCs demonstrated impaired migration out of the epidermis. Whole-transcriptome analyses revealed that genes that promoted cell adhesion were highly expressed, but CCR7 was downregulated in CTCF-depleted LCs. Hapten-induced contact hypersensitivity responses were more sustained in LC-specific CTCF-deficient mice, whereas epicutaneous sensitization to protein antigen was attenuated, indicating that CTCF-dependent LC homeostasis is required for optimal immune function of LCs in a context-dependent manner. CONCLUSION: Our results show that CTCF positively regulates the homeostatic pool and the efficient emigration of LCs, which are required for modulating the functional immune network of the skin.
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실)
1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Yonsei Cardiovascular Research Institute (심혈관연구소)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
Yonsei Authors
김태균(Kim, Tae Kyun) ; 김형표(Kim, Hyoung Pyo) ; 박채규(Park, Chae Gyu) ; 송민지(Song, Min Ji) ; 이민걸(Lee, Min Geol) ; 이종주(Lee, Jong Joo) ; 정연욱(Chung, Youn Wook)
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