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박채규(의생명과학부) 이민걸(피부과학교실) J Invest Dermatol
등록일 : 2017-11-17 오전 11:46:00       조회 : 977
첨   부 :
제1저자 김태균(피부과학교실)
교신저자 박채규(의생명과학부, BK21) 이민걸(피부과학교실, BK21)

J Invest Dermatol. 2017 Nov 11. pii: S0022-202X(17)33152-4. doi: 10.1016/j.jid.2017.11.003. [Epub ahead of print]
Skin-Specific CD301b+ Dermal Dendritic Cells Drive IL-17-Mediated Psoriasis-Like Immune Response in Mice.
Kim TG1, Kim SH1, Park J2, Choi W3, Sohn M3, Na HY4, Lee M1, Lee JW1, Kim SM5, Kim DY1, Kim HP6, Choi JH7, Park CG8, Lee MG9.

Author information
1Department of Dermatology, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, South Korea.2Department of Dermatology, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, South Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.3Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea.4Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea.5Department of Dermatology, National Health Insurance Service Ilsan Hospital, Goyang, South Korea.6Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea; Department of Environmental Medical Biology, Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul, South Korea.7Department of Life Science, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul, South Korea.8Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: CHAEGYU@yuhs.ac.9Department of Dermatology, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, South Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: MGLEE@yuhs.ac.

Abstract

Conventional dendritic cells (cDCs) are composed of heterogeneous subsets commonly arising from DC-committed progenitors. A population of CD301b-expressing DCs has recently been identified in non-lymphoid barrier tissues such as skin. However, whether CD301b+ DCs in the skin represent ontogenetically unique subpopulation of migratory cDCs has not been fully addressed. Here, we demonstrated that CD301b+ dermal DCs were distinct subpopulation of FLT3L-dependent CD11b+ cDC2 lineage which required an additional GM-CSF cue for the adequate development. Although the majority of lymphoid resident cDC2 lacked CD301b expression, dermal migratory cDC2 contained a substantial fraction of CD301b+ subset. Similar to CD301b- population, CD301b+ dermal DC development was closely regulated by FLT3 signaling, suggesting their common origin from FLT3L-responsive cDC progenitors. However, FLT3L-driven cDC progenitor culture was not sufficient but additional GM-CSF treatment was required to produce CD301b+ cDC2. In vivo development of CD301b+ cDC2 was significantly augmented by exogenous GM-CSF, while the repopulation of CD301b+ dermal cDC2 was abrogated by GM-CSF neutralization. Functionally, CD301b+ cDC2 was capable of producing a high level of IL-23, and the depletion of CD301b+ cDC2 effectively prevented IL-17-mediated psoriasiform dermatitis. Therefore, our findings highlight the differentiation program of a distinct CD301b+ dermal cDC2 subset in the skin and its involvement in psoriatic inflammation.
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