Cutting edge: Anti–TIM-3 treatment exacerbates pulmonary inflammation and fibrosis in mice

Takuma Isshiki, Hisaya Akiba, Masafumi Nakayama, Norihiro Harada, Ko Okumura, Sakae Homma, Sachiko Miyake

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Promising results of immune checkpoint inhibitors have indicated the use of immunotherapy against malignant tumors. However, they cause serious side effects, including autoimmune diseases and pneumonitis. T cell Ig and mucin domain (TIM)-3 is a new candidate immune checkpoint molecule; however, the potential toxicity associated with anti–TIM-3 treatment is unknown. In this study, we investigated the pathological contribution of anti–TIM-3 mAb in a bleomycin-induced lung inflammation and fibrosis model. Anti–TIM-3–treated mice showed more severe inflammation and peribronchiolar fibrosis compared with control IgG-treated mice. Anti–TIM-3 mAb was associated with increased numbers of myofibroblasts, collagen deposition, and TGF-b1 production in lungs. TIM-3 expression was only detected on alveolar macrophages that protect against fibrosis by apoptotic cell clearance. Treatment with anti–TIM-3 mAb inhibited the phagocytic ability of alveolar macrophages in vivo, resulting in the defective clearance of apoptotic cells in lungs. In summary, anti–TIM-3 mAb treatment might cause pneumonitis and it should be used with caution in clinical settings.

Original languageEnglish
Pages (from-to)3733-3737
Number of pages5
JournalJournal of Immunology
Volume199
Issue number11
DOIs
Publication statusPublished - 2017 Dec 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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