Dantas, Rafael Leite, Masemann, Doerthe, Schied, Tanja, Bergmeier, Vera, Vogl, Thomas, Loser, Karin, Brachvogel, Bent, Varga, Georg, Ludwig, Stephan ORCID: 0000-0003-4490-3052 and Wixler, Viktor (2016). Macrophage-mediated psoriasis can be suppressed by regulatory T lymphocytes. J. Pathol., 240 (3). S. 366 - 378. HOBOKEN: WILEY. ISSN 1096-9896

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Abstract

We recently described an inducible human TNF transgenic mouse line (ihTNFtg) that develops psoriasis-like arthritis after doxycycline stimulation and analysed the pathogenesis of arthritis in detail. Here, we show that the skin phenotype of these mice is characterized by hyperproliferation and aberrant activation of keratinocytes, induction of pro-inflammatory cytokines, and infiltration with Th1 and Treg lymphocytes, particularly with macrophage infiltration into lesional skin, thus pointing to a psoriasis-like phenotype. To reveal the contribution of T cells and macrophages to the development of TNF-mediated psoriasis, ihTNFtg mice were crossbred into RAG1(KO) mice lacking mature T and B cells. Surprisingly, the psoriatic phenotype in the double mutants was not reduced; rather, it was enhanced. The skin showed significantly increased inflammation and in particular, increased infiltration by macrophages. Consequently, depletion of macrophages in RAG1(KO) or wild-type mice led to decreased disease severity. On the contrary, depletion of Treg cells in wild-type mice increased both psoriasis and the number of infiltrating macrophages, while adoptive transfer of Foxp3-positive cells into RAG1(KO) or wild-type mice decreased both the development of psoriasis and macrophage infiltration. Thus, we conclude that Treg lymphocytes inhibit the pro-inflammatory activity of macrophages, which are the major immune effector cells in hTNF-mediated psoriasis. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Linked Commentary: .

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Dantas, Rafael LeiteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Masemann, DoertheUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schied, TanjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bergmeier, VeraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vogl, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loser, KarinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brachvogel, BentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Varga, GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ludwig, StephanUNSPECIFIEDorcid.org/0000-0003-4490-3052UNSPECIFIED
Wixler, ViktorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-257850
DOI: 10.1002/path.4786
Journal or Publication Title: J. Pathol.
Volume: 240
Number: 3
Page Range: S. 366 - 378
Date: 2016
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1096-9896
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TUMOR-NECROSIS-FACTOR; MURINE MODEL; CELLS CONTROL; EXPRESSION; ACTIVATION; RECEPTOR; TNF; PATHOGENESIS; S100A12; MRP14Multiple languages
Oncology; PathologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/25785

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