Rare Group of T-Cells Trigger and Sustain Pulmonary Fibrosis in Mice, Study Finds

Rare Group of T-Cells Trigger and Sustain Pulmonary Fibrosis in Mice, Study Finds

A rare form of immune T-cells promotes chronic inflammation and pulmonary fibrosis, researchers at the Johns Hopkins University School of Medicine found. Their discovery, made in a mice model of the disease, may lead to a new therapeutic target for lung fibrosis.

The research report, Deletion of mTORC1 activity in CD4+ T cells is associated with lung fibrosis and increased γδ T cells, appeared in the journal PLOS one.

Pulmonary fibrosis is an end stage of a number of chronic inflammatory lung diseases, in which the lungs become scarred and breathing becomes increasingly difficult. The condition can be caused by environmental factors, like exposure to cigarette smoke and air pollution, or, as in idiopathic pulmonary fibrosis, results from causes unknown.

Previous studies have shown that enhanced levels of the pro-inflammatory cytokine IL-17A are a key factor in promoting chronic inflammation and pulmonary fibrosis. Mice deficient in IL-17A are known to develop less fibrosis, and therapies reducing this cytokine levels are able to disrupt and even reverse fibrosis.

IL-17A is produced by T helper 17 cells (Th17). The research team studied mutant mice, lacking Th17 cells, to see if they were protected from developing fibrosis in the lungs.

Researchers used a common animal model to induce pulmonary fibrosis, where both normal and mutant mice were repeatedly injected with bleomycin for four weeks. Bleomycin is a human chemotherapeutic agent that can induce fibrosis.

Researchers expected the mutant mice, lacking Th17 cells, to be protected from developing fibrosis, but instead found increased fibrosis and death among these animals. Further investigation unexpectedly revealed a robust production of IL-17A in their lungs, produced and maintained by a rare form of T-cells called gamma delta T-cells (γδ T-cells).

The antigen activating γδ T-cells is still largely unknown, but the cytotoxic effect of this form of T-cells toward a broad range of cells has already made them a promising target of immunotherapy in a variety of solid and hematological cancers.

The study’s results revealed the critical role of γδ T-cells in IL-17A production, and highlighted the importance of targeting both Th17 cells and γδ T-cells within the lungs to possibly treat pulmonary fibrosis.

“Targeting these γδ T cells specifically and altering their cytokine production away from IL-17A and towards a phenotype that has been shown to be protective, could represent a novel therapeutic avenue,” the team concluded.

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