Cutting Edge: Anti-TIM-3 Treatment Exacerbates Pulmonary Inflammation and Fibrosis in Mice.
J Immunol
; 199(11): 3733-3737, 2017 12 01.
Article
em En
| MEDLINE
| ID: mdl-29061768
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-ß1 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pneumonia
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Fibrose Pulmonar
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Macrófagos Alveolares
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Receptor Celular 2 do Vírus da Hepatite A
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Imunoterapia
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Pulmão
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Anticorpos Monoclonais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article