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

Title
Skin-Specific CD301b(+) Dermal Dendritic Cells Drive IL-17-Mediated Psoriasis-Like Immune Response in Mice
Author
최재훈
Keywords
BONE-MARROW CULTURES; DELTA T-CELLS; COLONY-STIMULATING FACTOR; HIGH-DIMENSIONAL ANALYSIS; LANGERHANS CELLS; IN-VIVO; GM-CSF; PLAQUE-FORMATION; HOMEOSTASIS; DIFFERENTIATION
Issue Date
2018-04
Publisher
ELSEVIER SCIENCE INC
Citation
JOURNAL OF INVESTIGATIVE DERMATOLOGY, v. 138, no. 4, page. 844-853
Abstract
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 CD3011D(+) DCs in the skin represent an ontogenetically unique subpopulation of migratory cDCs has not been fully addressed. Here, we demonstrated that CD3011D(+) dermal DCs were distinct subpopulation of FMS-like tyrosine kinase 3 ligand (FLT3L) dependent CD111D(+) 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 CD3011D(+) subset. Similar to CD301b- population, CD3011D(+) 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 CD3011D(+) cDC2. In vivo development of CD3011D(+) cDC2 was significantly augmented by exogenous GM-CSF, while the repopulation of CD3011D(+) dermal cDC2 was abrogated by GM-CSF neutralization. Functionally, CD3011D(+) cDC2 was capable of producing a high level of IL-23, and the depletion of CD3011D(+) cDC2 effectively prevented IL-17 mediated psoriasiform dermatitis. Therefore, our findings highlight the differentiation program of a distinct CD3011D(+) dermal cDC2 subset in the skin and its involvement in psoriatic inflammation.
URI
https://www.jidonline.org/article/S0022-202X(17)33152-4/fulltexthttp://repository.hanyang.ac.kr/handle/20.500.11754/118292
ISSN
0022-202X; 1523-1747
DOI
10.1016/j.jid.2017.11.003
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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