Allies or enemies? The effect of regulatory T cells and related T lymphocytes on the profibrotic environment in bleomycin-injured lung mouse models.

Mutlu, Seyran; Scalise, Melanie; Philip, Stumbles; Gazdhar, Amiq; Blank, Fabian (2023). Allies or enemies? The effect of regulatory T cells and related T lymphocytes on the profibrotic environment in bleomycin-injured lung mouse models. Clinical and experimental medicine, 23(4), pp. 1075-1088. Springer 10.1007/s10238-022-00945-7

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Idiopathic pulmonary fibrosis (IPF) is characterized by permanent scarring of lung tissue and declining lung function, and is an incurable disease with increase in prevalence over the past decade. The current consensus is that aberrant wound healing following repeated injuries to the pulmonary epithelium is the most probable cause of IPF, with various immune inflammatory pathways having been reported to impact disease pathogenesis. While the role of immune cells, specifically T lymphocytes and regulatory T cells (Treg), in IPF pathogenesis has been reported and discussed recently, the pathogenic or beneficial roles of these cells in inducing or preventing lung fibrosis is still debated. This lack of understanding could be due in part to the difficulty in obtaining diseased human lung tissue for research purposes. For this reason, many animal models have been developed over the years to attempt to mimic the main clinical hallmarks of IPF: among these, inducing lung injury in rodents with the anti-cancer agent bleomycin has now become the most commonly studied animal model of IPF. Pulmonary fibrosis is the major side effect when bleomycin is administered for cancer treatment in human patients, and a similar effect can be observed after intra-tracheal administration of bleomycin to rodents. Despite many pathophysiological pathways of lung fibrosis having been investigated in bleomycin-injured animal models, one central facet still remains controversial, namely the involvement of specific T lymphocyte subsets, and in particular Treg, in disease pathogenesis. This review aims to summarize the major findings and conclusions regarding the involvement of immune cells and their receptors in the pathogenesis of IPF, and to elaborate on important parallels between animal models and the human disease. A more detailed understanding of the role of Treg and other immune cell subsets in lung injury and fibrosis derived from animal models is a critical basis for translating this knowledge to the development of new immune-based therapies for the treatment of human IPF.

Item Type:

Journal Article (Review Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology

UniBE Contributor:

Mutlu, Seyran Mathilde, Scalise, Melanie Cristine, Gazdhar, Amiq, Blank, Fabian

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1591-9528

Publisher:

Springer

Language:

English

Submitter:

Pubmed Import

Date Deposited:

22 Nov 2022 10:13

Last Modified:

01 Aug 2023 00:11

Publisher DOI:

10.1007/s10238-022-00945-7

PubMed ID:

36403186

Uncontrolled Keywords:

Bleomycin injury IPF Immunomodulatory effect Lung fibrosis Mouse lung injury model T cells

BORIS DOI:

10.48350/175017

URI:

https://boris.unibe.ch/id/eprint/175017

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