TGF-β1 limits the onset of innate lung inflammation by promoting mast cell-derived IL-6

Kirthana Ganeshan, Laura K. Johnston, Paul J. Bryce*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


TGF-β1 is an important suppressive mediator of inflammation, but it can also drive fibrosis and remodeling in the lung. In response to intratracheal LPS, neutrophils migrate into the lung, and TGF-β1 was suggested to protect against the ensuing injury. However, the mechanisms for this protective role remain unknown. Using a model of acute lung injury, we demonstrate that TGF-β1 decreases neutrophil numbers during the onset of injury. This was due to increased apoptosis rather than reduced migration. We demonstrate that TGF-β1 does not directly regulate neutrophil apoptosis but instead functions through IL-6 to promote neutrophil clearance. rIL-6 is sufficient to promote neutrophil apoptosis and reduce neutrophilia in bronchoalveolar lavage fluid, while IL-6 increases rapidly following LPS-induced injury. Mast cells are a critical source of IL-6, because mast cell-deficient mice exhibit increased neutrophil numbers that are reduced by reconstitution with wild-type, but not IL-6-/-, mast cells. Although IL-6 diminishes neutrophilia in mast cell-deficient mice, TGF-β1 is ineffective, suggesting that these effects were mast cell dependent. Taken together, our findings establish a novel pathway through which TGF-β1, likely derived from resident regulatory T cells, controls the severity and magnitude of early innate inflammation by promoting IL-6 from mast cells.

Original languageEnglish (US)
Pages (from-to)5731-5738
Number of pages8
JournalJournal of Immunology
Issue number11
StatePublished - Jun 1 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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