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Skin-Specific CD301b(+) Dermal Dendritic Cells Drive IL-17-Mediated Psoriasis-Like Immune Response in Mice

 Tae-Gyun Kim  ;  Sung Hee Kim  ;  Jeyun Park  ;  Wanho Choi  ;  Moah Sohn  ;  Hye Young Na  ;  Minseok Lee  ;  Jae Won Lee  ;  Soo Min Kim  ;  Do-Young Kim  ;  Hyoung-Pyo Kim  ;  Jae-Hoon Choi  ;  Chae Gyu Park  ;  Min-Geol Lee 
 Journal of Investigative Dermatology, Vol.138(4) : 844-853, 2018 
Journal Title
 Journal of Investigative Dermatology 
Issue Date
Conventional dendritic cells (cDCs) are composed of heterogeneous subsets commonly arising from dendritic cell (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 an ontogenetically unique subpopulation of migratory cDCs has not been fully addressed. Here, we demonstrated that CD301b(+) dermal DCs were distinct subpopulation of FMS-like tyrosine kinase 3 ligand (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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1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kim, Do Young(김도영) ORCID logo https://orcid.org/0000-0002-0194-9854
Kim, Tae-Gyun(김태균) ORCID logo https://orcid.org/0000-0002-2116-4579
Kim, Hyoung Pyo(김형표) ORCID logo https://orcid.org/0000-0003-1441-8822
Na, Hye Young(나혜영) ORCID logo https://orcid.org/0000-0002-2886-9926
Park, Chae Gyu(박채규) ORCID logo https://orcid.org/0000-0003-1906-1308
Lee, Min Geol(이민걸) ORCID logo https://orcid.org/0000-0001-7040-5335
Lee, Jae Won(이재원)
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