Feb 9, 2012

OX40/OX40 ligand interactions in T-cell regulation and asthma

Chest
Davinder Kaur, Christopher Brightling

Abstract

The OX40 receptor is preferentially expressed by T cells, and its cognate ligand OX40L is primarily expressed by antigen-presenting cells such as dendritic cells following activation by thymic stromal lymphopoietin (TSLP). TSLP is released by the bronchial epithelium, airway smooth muscle, and some inflammatory cells in response to numerous insults such as allergens, viruses, and physical damage. OX40L is a costimulatory molecule that plays a sentinel role in the adaptive immune response by promoting T helper (Th) 2 polarization of naive T cells within the lymph node. These polarized T cells produce Th2 cytokines such as IL-4, IL-5, and IL-13, which have been implicated particularly in allergic eosinophilic asthma. Animal models have positioned both TSLP and OX40/OX40L as critical in the development of airway inflammation and hyperreactivity. In human disease, there is good evidence that TSLP is upregulated in asthma, but there are limited data to demonstrate overexpression of OX40 or OX40L in disease. Targeting the OX40/OX40L axis or TSLP presents a novel therapeutic strategy that has the potential of modifying the disease process and, therefore, impacting on its natural history. Whether this approach can demonstrate efficacy ...Continue Reading

  • References40
  • Citations31

Citations

Mentioned in this Paper

TSLP protein, human
T-Lymphocyte
TNFRSF4
Recombinant OX40 Ligand
Antigen-Presenting Cells
TNFSF4
OX40 Receptors
Recombinant Interleukin-5
Smooth Muscle
Tslpr protein, mouse

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