Macrophage-mediated psoriasis can be suppressed by regulatory T lymphocytes

作者：Dantas Rafael Leite; Masemann Doerthe; Schied Tanja; Bergmeier Vera; Vogl Thomas; Loser Karin; Brachvogel Bent; Varga Georg; Ludwig Stephan; Wixler Viktor

来源：Journal of Pathology, 2016, 240(3): 366-377.

DOI：10.1002/path.4786

<jats:title>Abstract</jats:title><jats:p>We recently described an inducible human <jats:styled-content style="fixed-case">TNF</jats:styled-content> transgenic mouse line (<jats:styled-content style="fixed-case">ihTNFtg</jats:styled-content>) 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 <jats:styled-content style="fixed-case">TNF</jats:styled-content>‐mediated psoriasis, <jats:styled-content style="fixed-case">ihTNFtg</jats:styled-content> mice were crossbred into <jats:styled-content style="fixed-case">RAG1<jats:sup>KO</jats:sup></jats:styled-content> 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 <jats:styled-content style="fixed-case">RAG1<jats:sup>KO</jats:sup></jats:styled-content> 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 <jats:styled-content style="fixed-case">RAG1<jats:sup>KO</jats:sup></jats:styled-content> 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 <jats:styled-content style="fixed-case">hTNF</jats:styled-content>‐mediated psoriasis.

• 出版日期2016-11