Tryptophan catabolites regulate mucosal sensitization to ovalbumin in respiratory airways

Allergy
S O OdemuyiwaR Moqbel

Abstract

Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in tryptophan catabolism, is important in generating tolerance at the foetal-maternal interface. Studies using 1-methyl-tryptophan (1-MT), the specific inhibitor of IDO, showed that this enzyme is important in interferon-gamma (IFN-gamma)-dependent inhibition of allergic inflammation in the respiratory airway during immunotherapy. We investigated the role of IDO in the development of allergic sensitization, leading to allergic inflammation and airway hyper-responsiveness (AHR). We used a mouse model to generate mucosal tolerance to lipopolysaccharide-free ovalbumin (OVA) following repeated intranasal inoculation of OVA over a 3-day period. We tested the successful induction of tolerance by subsequent intraperitoneal (i.p.) sensitization followed by intranasal challenge with OVA. A slow-release pellet of 1-MT implanted into mice was used to block IDO activity prior to repeated intranasal inoculation of OVA. We measured T-cell proliferation in response to OVA, determined airway inflammation, and measured AHR to intranasal methacholine to investigate the role of IDO in sensitization to OVA. Repeated intranasal administration of OVA generated tolerance and prevented a subs...Continue Reading

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Citations

Sep 29, 2012·Immunological Investigations·Theodore S Johnson, David H Munn
Oct 7, 2010·Expert Review of Respiratory Medicine·Kanami OriharaRedwan Moqbel
Jan 24, 2015·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·J L AtherM E Poynter
Jul 18, 2015·Clinical Science·Amanda W S YeungShane R Thomas
Jul 9, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Pierre-Joseph RoyerAmir M Ghaemmaghami

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