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CCR4 Involvement in the Expansion of T Helper Type 17 Cells in a Mouse Model of Psoriasis.
- Source :
-
The Journal of investigative dermatology [J Invest Dermatol] 2021 Aug; Vol. 141 (8), pp. 1985-1994. Date of Electronic Publication: 2021 Mar 02. - Publication Year :
- 2021
-
Abstract
- Psoriasis is a chronic skin disease associated with T helper (Th)17-mediated inflammation. Because CCR4 is a major chemokine receptor expressed on Th17 cells, we investigated the role of CCR4 in a modified imiquimod-induced psoriasis model that showed enhanced skin infiltration of Th17 cells. CCR4-deficient mice had less severe skin disease than wild-type mice. Th17 cells were decreased in the skin lesions and regional lymph nodes of CCR4-deficient mice. In the regional lymph nodes of wild-type mice, CD44 <superscript>+</superscript> memory Th17 cells expressing CCR4 were found to be clustered with dendritic cells expressing CCL22, a ligand for CCR4. Such dendritic cell‒Th17 cell clusters were significantly decreased in CCR4-deficient mice. Similar results were obtained using the IL-23‒induced psoriasis model. In vitro, compound 22, a CCR4 antagonist, significantly reduced the expansion of Th17 cells in the coculture of CD11c <superscript>+</superscript> dendritic cells and CD4 <superscript>+</superscript> T cells separately prepared from the regional lymph nodes of wild-type mice with psoriasis. In vivo, compound 22 ameliorated the psoriasis-like skin disease in wild-type mice with significant decreases of Th17 cells in the regional lymph nodes and skin lesions. Collectively, CCR4 is likely to play a role in the pathogenesis of psoriasis through the expansion of Th17 cells.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cell Communication drug effects
Cell Communication immunology
Cell Proliferation drug effects
Cells, Cultured
Coculture Techniques
Dendritic Cells immunology
Disease Models, Animal
Humans
Imiquimod administration & dosage
Imiquimod immunology
Mice
Mice, Transgenic
Primary Cell Culture
Psoriasis drug therapy
Psoriasis pathology
Receptors, CCR4 antagonists & inhibitors
Receptors, CCR4 genetics
Skin immunology
Th17 Cells drug effects
Th17 Cells metabolism
Psoriasis immunology
Receptors, CCR4 metabolism
Skin pathology
Th17 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1523-1747
- Volume :
- 141
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The Journal of investigative dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 33662381
- Full Text :
- https://doi.org/10.1016/j.jid.2020.12.034