Immunosuppressive regulatory T cells promote experimental lung fibrosis by producing growth factors
(2011)
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- Authors
- Supervisors
- Huaux, François
- Abstract
- (en) While there are numerous studies showing that fibrogenesis is linked to the presence of CD4+ effector T lymphocytes (T eff or Th, helper), the role of Th17 cells and the immunological balance between CD4+ regulatory T lymphocytes (T regs) and T eff cells in fibrogenesis remains to be determined. With this work, we explored the possible implication of inflammatory Th17 and immunosuppressive T regs in the development of fibrosis in a mouse model of chronic lung inflammation and fibrosis induced by silica particles. We first demonstrated that macrophage-derived IL-23 induced a rapid lung recruitment of IL-17A- and IL-22-producing T eff cells in response to silica particles. Through the production of IL-17A, these cells contributed to the development of early alveolitis by exacerbating the release of pro-inflammatory cytokines (IL-1β and IL-6) and chemokines (KC and MIP-2). However, neither Th17-related cytokine deficiency nor steroid treatment limited late lung fibrosis. We next observed that silica-induced early alveolitis was followed by a marked accumulation of CD4+ Foxp3+ T regs in the lungs and demonstrated that these immunosuppressive T cells are recruited to limit pulmonary inflammation and fibrosis by inhibiting excessive T eff activities and cytokines. However, the persistent influx of T regs also contributed to the development of lung fibrosis since T regs produced high levels of PDGF-B and TGF-β1, which in turn, stimulated fibroblast proliferation and increased lung collagen deposition. Altogether, our data propose the new concept that beside T eff lymphocytic inflammation and sustained expression of T eff cell secreted profibrotic cytokines, an alternative and apparently paradoxical mechanism of fibrosis exists: immunosuppressive regulatory T lymphocytes persistently recruited to limit the establishment of inflammation participate in the development of lung fibrosis by producing growth factors.
- Affiliations
Citations
Lo Re, S. (2011). Immunosuppressive regulatory T cells promote experimental lung fibrosis by producing growth factors. https://hdl.handle.net/2078.5/39754