Alleviating Allergies

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Science  27 Apr 2007:
Vol. 316, Issue 5824, pp. 517
DOI: 10.1126/science.316.5824.517b

The aberrant activation of T helper 2 CD4+ lymphocytes can result in damaging allergic responses, and hence a great deal of effort has been directed toward understanding the mechanisms that normally regulate these cells. Grohmann et al. show that a soluble form of the glucocorticoid-inducible tumor necrosis factor receptor (GITR) cross-regulates allergic responses in mice by signaling through its own ligand. This causes plasmacytoid dendritic cells (pDCs) to produce indoleamine 2,3-dioxygenase (IDO), which mediates strong immunomodulatory effects though the catabolism of tryptophan. Administration of the synthetic glucocorticoid dexamethasone reduced symptoms of allergic responses in mice, including airway inflammation, and this effect depended on GITR-induced IDO, suggesting that this pathway may promote some actions of corticosteroids. In another study, Xanthou et al. observed that the regulatory cytokine osteopontin is expressed in the lungs of asthma patients and can directly affect allergic airway inflammation in mice, again via the activities of pDCs. In this system, however, allergic responses were promoted by osteopontin during the primary phase of antigen challenge, whereas it exerted an anti-inflammatory influence during secondary challenge. The two mediators identified in these studies—GITR-induced IDO and osteopontin—may offer targets for the treatment of asthma. — SJS

Nat. Med. 13, 10.1038/nm1563; 10.1038/nm1580 (2007).

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