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Lymphotoxin β receptor signaling mediates the formation of high endothelial venule-like vessels in atopic dermatitis-like skin lesions in mice
High endothelial venules (HEVs) are specialized blood vessels contribute to the trafficking of lymphocytes into secondary lymphoid organs by expressing a group of L-selectin ligands called peripheral node addressins (PNAd). In lymph nodes (LNs), lymphotoxin β receptor (LTβR) signaling from dendritic...
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Published in: | The Journal of immunology (1950) 2022-05, Vol.208 (1_Supplement), p.48-48.06 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | High endothelial venules (HEVs) are specialized blood vessels contribute to the trafficking of lymphocytes into secondary lymphoid organs by expressing a group of L-selectin ligands called peripheral node addressins (PNAd). In lymph nodes (LNs), lymphotoxin β receptor (LTβR) signaling from dendritic cells (DCs) is essential for the formation of HEVs. On the other hand, PNAd+ HEV-like vessels are observed in the skin under certain inflammatory conditions, such as atopic dermatitis (AD). However, the characteristics and the formation mechanism of HEV-like vessels in the inflammatory skin remains unclear. To address these issues, we first identified PNAd+ HEV-like vessels in the skin using a calcipotriol-induced mouse AD model. HEV-like vessels were located in the postcapillary venules abundant in cellular organelles, which were similar to HEVs in LNs. Blockade of LTβR-signaling by administration of LTβR-Fc fusion protein markedly decreased the formation of HEV-like vessels in the AD-like skin. Analysis using published single-cell RNA-seq data of human AD skin revealed that T cells and DCs highly expressed LTB, a gene encoding LTβ. The expression of LTB was highlighted in T cells by RNAscope in both human AD lesions and mouse AD-like skin. The formation of HEV-like vessels in AD-like skin was normal in Ltbfl/flCD11cCre mice, but was partially impaired in Ltbfl/flCD4Cre mice. Collectively, HEV-like vessels in the inflammatory skin show similar characteristics to HEVs in LNs, and LTβR signaling, partly by LTβ from T cells, is responsible for their formation. |
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ISSN: | 0022-1767 1550-6606 |
DOI: | 10.4049/jimmunol.208.Supp.48.06 |