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

14 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

Fingerprint

Dive into the research topics of 'Cutting edge: Anti–TIM-3 treatment exacerbates pulmonary inflammation and fibrosis in mice'. Together they form a unique fingerprint.

Cite this