Journal
JOURNAL OF IMMUNOLOGY
Volume 199, Issue 11, Pages 3733-3737Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1700059
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Funding
- Japan Society for the Promotion of Science KAKENHI [JP16K09924, JP26293087]
- Grants-in-Aid for Scientific Research [16K09554, 16K15112, 16H02960, 16K09587, 17H04218] Funding Source: KAKEN
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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-beta 1 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.
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