title: Potential immunologic targets for treating fibrosis in systemic sclerosis: a review focused on leukocytes and cytokines.
abstract: OBJECTIVE
  Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis. Although the pathogenesis remains unclear, a variety of cells contribute to the fibrotic process via interactions with each other and production of various cytokines. Recent literature related to the immunologic pathogenesis and future strategies for treating the fibrosis of SSc are discussed and, especially, this literature-based review that includes the authors' perspective, focused on leukocytes and cytokines.
  
  
  METHODS
  A PubMed search for articles published between January 2005 and January 2012 was conducted using the following keywords: systemic sclerosis, leukocyte, cytokine, growth factor, and chemokine. The reference lists of identified articles were searched for further articles.
  
  
  RESULTS
  Targeting profibrogenic cytokines, including transforming growth factor-β, is still a very active area of research in SSc and most cellular studies have focused on the roles of fibroblasts in SSc. However, a growing number of recent studies indicate a role for B cells in the development of SSc and other autoimmune diseases such as systemic lupus erythematosus. Therefore, B-cell-targeted therapies, including currently available monoclonal antibodies against CD19, CD20, CD22, and B-cell-activating factor, belonging to the tumor necrosis factor family represent possible treatment options. Furthermore, the modulation of T-cell costimulatory molecules such as a recombinant fusion protein of cytotoxic T-lymphocyte antigen-4 may be as effective in SSc as it is in treating other autoimmune diseases. Approaches to antagonize interleukin (IL)-1, IL-6, or IL-17A signaling may also be attractive.
  
  
  CONCLUSIONS
  This review describes recent advances in the treatment of fibrosis in SSc patients focused on immunologic strategies, such as leukocyte- or cytokine-targeted therapies.
authors.affiliation: Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan. minoruha@derma.m.kanazawa-u.ac.jp
authors.forename: Minoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takehara
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005355:Fibrosis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007378:Interleukins / Q000037:antagonists & inhibitors; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D007378:Interleukins