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Updated: Jun 11, 2026
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Induction of Mouse Lung Injury by Endotracheal Injection of Bleomycin
Published on: April 30, 2019
Cell adhesion molecules regulate fibrotic process via Th1/Th2/Th17 cell balance in a bleomycin-induced scleroderma
Ayumi Yoshizaki1, Koichi Yanaba, Yohei Iwata
1Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Journal of Immunology (Baltimore, Md. : 1950)
|July 14, 2010
Summary
Adhesion molecules like L-selectin and ICAM-1 are crucial in bleomycin-induced fibrosis by regulating T-helper cell infiltration. Their absence inhibits fibrosis, while other molecules like P-selectin promote it.
Area of Science:
- Immunology
- Pathophysiology
- Fibrosis research
Background:
- Systemic sclerosis is modeled in mice using bleomycin, inducing skin and lung fibrosis via inflammatory cell infiltration.
- Adhesion molecules are key regulators in this fibrotic process, independent of antigen sensitization.
Purpose of the Study:
- To investigate the specific roles of various adhesion molecules in the pathogenesis of bleomycin-induced fibrosis.
- To determine how deficiencies in selectins, ICAM-1, and PSGL-1 affect T-helper cell responses and fibrotic outcomes.
Main Methods:
- Utilized a mouse model of bleomycin-induced skin and lung fibrosis.
- Examined the effects of genetic deficiencies in L-selectin, ICAM-1, P-selectin, E-selectin, and PSGL-1 on fibrotic development.
- Analyzed T-helper cell populations (Th1, Th2, Th17) and their cytokine profiles in affected tissues and bronchoalveolar lavage fluid.
Main Results:
- L-selectin and ICAM-1 deficiency reduced fibrosis, Th2/Th17 cytokines, and cell numbers, while increasing Th1 cytokines.
- P-selectin, E-selectin, or PSGL-1 deficiency exacerbated fibrosis, increasing Th2/Th17 cytokines/cells and decreasing Th1 cytokines.
- Differential expression of PSGL-1 and LFA-1 on Th1 versus Th2/Th17 cells was observed, correlating with their infiltration patterns.
Conclusions:
- L-selectin and ICAM-1 mediate fibrosis by promoting Th2 and Th17 cell accumulation in the skin and lungs.
- P-selectin, E-selectin, and PSGL-1 appear to regulate Th1 cell infiltration, which inhibits fibrosis development.
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