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Anti-fibrotic Drug Discovery is ideal for postgraduate students and researchers with an interest in anti-fibrotic drug discovery as well as clinicians specialising in liver, kidney, heart and lung disease, in which fibrosis plays a key role in pathology.
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Des études menées dans notre laboratoire ont montré que des réponses immunosuppressives accompagnent le développement de la fibrose pulmonaire induit par des particules de silice chez la souris. Ces réponses sont caractérisées par l'accumulation de lymphocytes T régulateurs et de macrophages produisant de l''IL-1O. Ces cellules participent au processus fibrotique en libérant des facteurs de croissance pour les fibroblastes. Dans cette étude, nous avons pu montrer qu'une nouvelle population de cellules immunosuppressives est recrutée après l'instillation de partiicules induisant de la fibrose. En effet, l'accumulation pulmonaire des Myeloid- Derived Suppressor Cells granulocytaires (G-M DSCs, CD 1 1b+, GR1+, Ly6G+) est intimement liée au développement progressif de la fibrose pulmonaire chez des souris traitées aux particules fibrosantes. Ces cellules immunorégulatrices possèdent la capacité d'inhiber la prolifération de lymphocytes T CD4 activés en libérant des facteurs solubles en co-culture. Nos résu ltats ont également montré que les MDSCs silicotiques n'activent pas directement les fibroblastes dans un modèle in vitro. Des études supplémentaires sont donc nécessaires pour identifier les médiateurs produits par les G-MDSCs silicotiques qui expliqueraient leur(s) rôle(s) potentiel (s) dans la fibrose. We have previously shown that immunosuppressive responses are associated with pulmonary fibrosis development induced by silica particles in mice. These responses are characterized by the lung accumulation of regulatory T lymphocytes and IL- 10-producing macrophages. These cells participate in the fibrotic process by releasing growth factors for fibroblasts. ln this study, we observed that a new immunosuppressive cell population is recruited into the lungs after particle instillation. Indeed, granulocytic Myeloid-Derived Suppressor Cells (G- MDSC, CD 11b+ , GR I + , Ly6G+ ) Jung accumulation is strongly associated with the establishment of particle-induced lung fibrosis These immunosuppressive cells possess the ability to suppress activated CD4 T cells proliferation in a co-culture system by releasing soluble factors. Our results showed that silicotic M DSC do not directly activate fibroblasts in vitro. Further studies are needed to identify mediators produced by MDSC which may explain their potential roles in Jung fibrosis.
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Cystic fibrosis, a genetic disorder in children and young adults, is a multisystemic disease that mainly affects the lungs. Advances and improvements in the diagnosis and management of this condition have led to increased overall and symptom-free survival in cystic fibrosis patients. This book examines recent advances in the field and presents an evidence-based approach to the management of cystic fibrosis.
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