Mer tyrosine kinase as a possible link between resolution of inflammation and tissue fibrosis in IgG4-related disease

Lucrezia Rovati, Naoki Kaneko, Federica Pedica, Antonella Monno, Takashi Maehara, Cory Perugino, Marco Lanzillotta, Simone Pecetta, John H. Stone, Claudio Doglioni, Angelo A. Manfredi, Shiv Pillai, Emanuel Della-Torre

研究成果: ジャーナルへの寄稿学術誌査読

3 被引用数 (Scopus)

抄録

Objectives: IgG4-related disease (IgG4-RD) is a systemic fibro-inflammatory disorder characterized by a dysregulated resolution of inflammation and wound healing response that might develop after an apoptotic insult induced by cytotoxic T lymphocytes (CTLs). Mer receptor tyrosine kinase (MerTK) and its ligand, protein S (ProS1), have a pivotal role in the resolution of inflammation, being implicated in the clearance of apoptotic cells, quenching of the immune response and development of tissue fibrosis. In the present work we aimed to investigate a possible involvement of the MerTK signalling pathway in the pathogenesis of IgG4-RD and development of tissue fibrosis. Methods: MerTK and ProS1 expression patterns in IgG4-RD lesions were evaluated by immunohistochemistry and immunofluorescence studies. Circulating MerTK+ monocytes, soluble Mer and MerTK ligands were measured in the peripheral blood of IgG4-RD patients and healthy controls by flow cytometry and ELISA, respectively. Results: MerTK was highly expressed by macrophages infiltrating IgG4-RD lesions. MerTK+ macrophages were more abundant in IgG4-RD than in Sjögren's syndrome and interacted with apoptotic cells and ProS1-expressing T and B lymphocytes. Moreover, they expressed the pro-fibrotic cytokine TGF-β and their numbers declined following rituximab-induced disease remission. Circulating MerTK+ monocytes, soluble Mer and MerTK ligands were not increased in the peripheral blood of patients with IgG4-RD. Conclusions: The MerTK-ProS1 axis is activated in IgG4-RD lesions, possibly leading to persistent stimulation of processes involved in the resolution of inflammation and tissue fibrosis.

本文言語英語
ページ(範囲)4929-4941
ページ数13
ジャーナルRheumatology (United Kingdom)
60
10
DOI
出版ステータス出版済み - 10月 1 2021

!!!All Science Journal Classification (ASJC) codes

  • リウマチ学
  • 薬理学(医学)

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