The expanding role of IL-7 and thymic stromal lymphopoietin as therapeutic target for rheumatoid arthritis

Expert Opin Ther Targets. 2014 May;18(5):581-94. doi: 10.1517/14728222.2014.893295. Epub 2014 Mar 18.

Abstract

Introduction: The discovery of IL-7 and thymic stromal lymphopoietin (TSLP) has been a major step in the understanding of arthritis. IL-7 amplifies the inflammation induced by other cytokines, primarily TNF. In animal models of arthritis, inhibition of IL-7 limits inflammation and joint erosion. TSLP is an IL-7-like cytokine that triggers dendritic cell-mediated Th2-type inflammatory responses and is considered as a master switch for allergic inflammation. TSLP is a downstream molecule of TNF-α and as such may be involved in the pathophysiology of inflammatory arthritis.

Areas covered: This review summarizes current knowledge of the role of IL-7 and TSLP derived from both animal models and studies in patients with rheumatoid arthritis (RA). The emergence of IL-7 blockade as a future therapy in RA is highlighted, along with the potential goals and limitations of this therapeutic approach. The write-up also highlights the functional capacities of TSLP in arthritis.

Expert opinion: Evidences suggest important roles for IL-7 and TSLP in the pathogenesis of RA and can be viewed as potential therapeutic targets. Regulation of these at genetic level is a promising investigational area. Given the difficulty in reconstituting T cells in patients with RA, therapeutic approaches that minimize the elimination of T cells are likely to be more desirable.

MeSH terms

  • Animals
  • Antirheumatic Agents / pharmacology*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / physiopathology
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Cytokines / antagonists & inhibitors*
  • Cytokines / genetics
  • Cytokines / physiology
  • Drug Evaluation, Preclinical
  • Gene Expression Regulation
  • Humans
  • Immunoglobulins / physiology
  • Interleukin-7 / antagonists & inhibitors*
  • Interleukin-7 / deficiency
  • Interleukin-7 / genetics
  • Interleukin-7 / pharmacology
  • Interleukin-7 / physiology
  • Macrophages / immunology
  • Mice
  • Mice, Knockout
  • Molecular Targeted Therapy*
  • Receptors, Cytokine / physiology
  • Receptors, Interleukin-7 / physiology
  • Selenium / pharmacology
  • Selenium / therapeutic use
  • Synovial Fluid / metabolism
  • Thymic Stromal Lymphopoietin

Substances

  • Antirheumatic Agents
  • CRLF2 protein, human
  • Cytokines
  • IL7 protein, human
  • Immunoglobulins
  • Interleukin-7
  • Receptors, Cytokine
  • Receptors, Interleukin-7
  • Tslpr protein, mouse
  • interleukin-7, mouse
  • Selenium
  • Thymic Stromal Lymphopoietin