2011
DOI: 10.1165/rcmb.2009-0167oc
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Airway Epithelial Indoleamine 2,3-Dioxygenase Inhibits CD4+T Cells duringAspergillus fumigatusAntigen Exposure

Abstract: Indoleamine 2,3-dioxygenase (IDO) suppresses the functions of CD4 1 T cells through its ability to metabolize the essential amino acid tryptophan. Although the activity of IDO is required for the immunosuppression of allergic airway disease by the Toll-LikeReceptor 9 (TLR9) agonist, oligonucleotides comprised of cytosine and guanine nucleotides linked by phosphodiester bonds (CpG) DNA, it is unclear whether IDO expression by resident lung epithelial cells is sufficient to elicit these effects. Therefore, we cr… Show more

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Cited by 31 publications
(25 citation statements)
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“…15 We found here that ECs contribute to the immunoregulatory function of IDO in vivo and may compensate for the lack of IDO on hematopoietic cells. This may accommodate the recent finding by Paveglio et al 19 showing the superior role of IDO1DCs in contributing to allergic airway inflammation. ECs activate IDO via TLR3, which is abundantly expressed both intracellularly and on the cell surface of ECs, 38 and IFN-c to which ECs also respond.…”
Section: Discussionsupporting
confidence: 78%
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“…15 We found here that ECs contribute to the immunoregulatory function of IDO in vivo and may compensate for the lack of IDO on hematopoietic cells. This may accommodate the recent finding by Paveglio et al 19 showing the superior role of IDO1DCs in contributing to allergic airway inflammation. ECs activate IDO via TLR3, which is abundantly expressed both intracellularly and on the cell surface of ECs, 38 and IFN-c to which ECs also respond.…”
Section: Discussionsupporting
confidence: 78%
“…10 Although ECs were found to induce Treg expansion, 13,14,40 restrained CD4 1 T-cell expansion in response to Aspergillus, 19 and produce IL-10 (this study), the therapeutic effects of kynurenines will undoubtedly cover IDO deficiency also in DCs. As a matter of fact, the highly polarized Th2/Th17 responses seen in Trif 2/2 mice are immunological features compatible with the functional program activated in lung DCs by the TRIF pathway.…”
Section: Discussionmentioning
confidence: 70%
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“…Evidence suggests that the airway epithelial cells are not simply "innocent bystanders" but may play a crucial role in innate and inflammatory responses 38 and in regulation of antimicrobial immunity. 39 Of great interest is the recent finding that the antifungal activity of epithelial cells occurs through signal transduction pathways leading to the induction of the indoleamine 2,3-dioxygenase enzyme, 40,41 known to play a pivotal role in regulation of pathogenic inflammatory responses to the fungus. 3 In conclusion, our findings highlight the multiple roles Dectin-1 may have in host resistance to Aspergillus that is probably achieved through distinct, yet complementary, mechanisms of immune resistance and tolerance that are dependent on the hematopoietic/ nonhematopoietic compartmentalization.…”
Section: Discussionmentioning
confidence: 99%
“…The production of IDO is strictly dependent on the presence of CD11c + DCs (Paveglio et al, 2011). Plasmacytoid DCs are another important target of CpG ODN, as they impact the development of eosinophilic airway inflammation by inducing the expression of the inhibitory costimulatory molecule PD L1, which is required for the generation of regulatory T cells (Kool et al, 2009).…”
Section: Effect Of Cpg Odn On the Mucosal Immune Systemmentioning
confidence: 99%