Carlo Chizzolini1. 1. Immunology and Allergy, University Hospital and School of Medicine, Geneva, Switzerland. Carlo.Chizzolini@unige.ch
Abstract
PURPOSE OF REVIEW: A better comprehension of the interactions between cells of the adaptive immune system with fibroblasts and endothelial cells is required to understand abnormal extracellular matrix deposition, development of pathologic fibrosis, and vasculopathy. RECENT FINDINGS: Skin T cells with high IL-4 production potential and peripheral blood T cells preferentially expressing chemokine receptors associated with Th2 functions are found in individuals with active systemic sclerosis. Animal models indicate that Th2 cells and IL-13 can induce muscular hypertrophy in pulmonary arterial vasculature. In bleomycin-induced fibrosis, B cells produce fibrogenic cytokines upon interaction of an endogenous ligand (hyaluronan) with toll-like receptor-4. In the sclerodermatous graft versus host model, the lack of tumor necrosis factor-production by CD4+ T cells is permissive for fibrosis development. Dermal fibrosis and capillary loss typical of systemic sclerosis can be reversible after high-dose immunosuppression and hematopoietic stem cell transplantation. SUMMARY: Although immunosuppressive strategies to treat patients with systemic sclerosis and allied conditions are largely disappointing, thus indicating a permissive rather than causative role of immunoinflammatory events characteristic of the disease, new findings stress that cells of the adaptive immune system play important roles in assisting fibrogenesis and vascular abnormalities. This may help in identifying efficacious strategies aimed at their control.
PURPOSE OF REVIEW: A better comprehension of the interactions between cells of the adaptive immune system with fibroblasts and endothelial cells is required to understand abnormal extracellular matrix deposition, development of pathologic fibrosis, and vasculopathy. RECENT FINDINGS: Skin T cells with high IL-4 production potential and peripheral blood T cells preferentially expressing chemokine receptors associated with Th2 functions are found in individuals with active systemic sclerosis. Animal models indicate that Th2 cells and IL-13 can induce muscular hypertrophy in pulmonary arterial vasculature. In bleomycin-induced fibrosis, B cells produce fibrogenic cytokines upon interaction of an endogenous ligand (hyaluronan) with toll-like receptor-4. In the sclerodermatous graft versus host model, the lack of tumor necrosis factor-production by CD4+ T cells is permissive for fibrosis development. Dermal fibrosis and capillary loss typical of systemic sclerosis can be reversible after high-dose immunosuppression and hematopoietic stem cell transplantation. SUMMARY: Although immunosuppressive strategies to treat patients with systemic sclerosis and allied conditions are largely disappointing, thus indicating a permissive rather than causative role of immunoinflammatory events characteristic of the disease, new findings stress that cells of the adaptive immune system play important roles in assisting fibrogenesis and vascular abnormalities. This may help in identifying efficacious strategies aimed at their control.
Authors: J Baraut; E I Grigore; F Jean-Louis; S H Khelifa; C Durand; F Verrecchia; D Farge; L Michel Journal: Bone Marrow Transplant Date: 2013-12-23 Impact factor: 5.483
Authors: Pravitt Gourh; Sandeep K Agarwal; Ezequiel Martin; Dipal Divecha; Blanca Rueda; Haley Bunting; Shervin Assassi; Gene Paz; Sanjay Shete; Terry McNearney; Hilda Draeger; John D Reveille; T R D J Radstake; Carmen P Simeon; Luis Rodriguez; Esther Vicente; Miguel A Gonzalez-Gay; Maureen D Mayes; Filemon K Tan; Javier Martin; Frank C Arnett Journal: J Autoimmun Date: 2009-09-30 Impact factor: 7.094