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, Mingeol Lee

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)844-853
Number of pages10
JournalJournal of Investigative Dermatology
Volume138
Issue number4
DOIs
Publication statusPublished - 2018 Apr 1

Fingerprint

Langerhans Cells
Granulocyte-Macrophage Colony-Stimulating Factor
Psoriasis
Skin
Protein-Tyrosine Kinases
Ligands
Dendritic Cells
Dermatitis
Interleukin-23
Tissue
Drive
Population
Cues
Inflammation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Kim, Tae Gyun ; Kim, Sung Hee ; Park, Jeyun ; Choi, Wanho ; Sohn, Moah ; Na, Hye Young ; Lee, Minseok ; Lee, Jae Won ; Kim, Soo Min ; Kim, Do Young ; Kim, Hyoung Pyo ; Choi, Jae Hoon ; Park, Chae Gyu ; Lee, Mingeol. / Skin-Specific CD301b + Dermal Dendritic Cells Drive IL-17−Mediated Psoriasis-Like Immune Response in Mice In: Journal of Investigative Dermatology. 2018 ; Vol. 138, No. 4. pp. 844-853.
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title = "Skin-Specific CD301b + Dermal Dendritic Cells Drive IL-17−Mediated Psoriasis-Like Immune Response in Mice",
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 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.",
author = "Kim, {Tae Gyun} and Kim, {Sung Hee} and Jeyun Park and Wanho Choi and Moah Sohn and Na, {Hye Young} and Minseok Lee and Lee, {Jae Won} and Kim, {Soo Min} and Kim, {Do Young} and Kim, {Hyoung Pyo} and Choi, {Jae Hoon} and Park, {Chae Gyu} and Mingeol Lee",
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Kim, TG, Kim, SH, Park, J, Choi, W, Sohn, M, Na, HY, Lee, M, Lee, JW, Kim, SM, Kim, DY, Kim, HP, Choi, JH, Park, CG & Lee, M 2018, ' Skin-Specific CD301b + Dermal Dendritic Cells Drive IL-17−Mediated Psoriasis-Like Immune Response in Mice ', Journal of Investigative Dermatology, vol. 138, no. 4, pp. 844-853. https://doi.org/10.1016/j.jid.2017.11.003

Skin-Specific CD301b + Dermal Dendritic Cells Drive IL-17−Mediated Psoriasis-Like Immune Response in Mice . / Kim, Tae Gyun; Kim, Sung Hee; Park, Jeyun; Choi, Wanho; Sohn, Moah; Na, Hye Young; Lee, Minseok; Lee, Jae Won; Kim, Soo Min; Kim, Do Young; Kim, Hyoung Pyo; Choi, Jae Hoon; Park, Chae Gyu; Lee, Mingeol.

In: Journal of Investigative Dermatology, Vol. 138, No. 4, 01.04.2018, p. 844-853.

Research output: Contribution to journalArticle

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T1 - Skin-Specific CD301b + Dermal Dendritic Cells Drive IL-17−Mediated Psoriasis-Like Immune Response in Mice

AU - Kim, Tae Gyun

AU - Kim, Sung Hee

AU - Park, Jeyun

AU - Choi, Wanho

AU - Sohn, Moah

AU - Na, Hye Young

AU - Lee, Minseok

AU - Lee, Jae Won

AU - Kim, Soo Min

AU - Kim, Do Young

AU - Kim, Hyoung Pyo

AU - Choi, Jae Hoon

AU - Park, Chae Gyu

AU - Lee, Mingeol

PY - 2018/4/1

Y1 - 2018/4/1

N2 - 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.

AB - 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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