Cellular and molecular mechanisms of TSLP function in human allergic disorders--TSLP programs the "Th2 code" in dendritic cells

Allergol Int. 2012 Mar;61(1):35-43. doi: 10.2332/allergolint.11-RAI-0376. Epub 2011 Dec 25.

Abstract

Thymic stromal lymphopoietin (TSLP) has been recently implicated as a key molecule for initiating allergic inflammation at the epithelial cell-dendritic cell (DC) interface. In humans, aberrant TSLP expression is observed in allergic tissues, such as lesional skins of atopic dermatitis, lungs of asthmatics, nasal mucosa of atopic rhinitis and nasal polyps, and ocular surface of allergic keratoconjunctivitis. TSLP is produced predominantly by damaged epithelial cells and stimulates myeloid DCs (mDCs). TSLP-activated mDCs can promote the differentiation of naïve CD4(+) T cells into a Th2 phenotype and the expansion of CD4(+) Th2 memory cells in a unique manner dependent on OX40L, one of the tumor necrosis factor superfamily members with Th2-promoting function, and lack of production of IL-12. From a genetic point of view, multiple genome-wide association studies have repeatedly identified the TSLP gene as one of the loci associated with susceptibility to allergic diseases. Thus, TSLP is a rational therapeutic target for the treatment of allergic disorders. Elucidating the mechanisms that regulate TSLP expression and the effects of TSLP on orchestrating the immune response toward a Th2 phenotype is essential for developing anti-TSLP therapy.

Publication types

  • Review

MeSH terms

  • Cytokines / metabolism
  • Cytokines / physiology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Humans
  • Hypersensitivity / immunology*
  • Hypersensitivity / metabolism
  • Inflammation / immunology
  • Inflammation / metabolism
  • OX40 Ligand / immunology
  • Receptors, Cytokine / metabolism
  • Signal Transduction
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism

Substances

  • CRLF2 protein, human
  • Cytokines
  • OX40 Ligand
  • Receptors, Cytokine
  • thymic stromal lymphopoietin