Altered Tryptophan Metabolism as a Paradigm for Good and Bad Aspects of Immune Privilege in Chronic Inflammatory Diseases

Li, Lingqian; Huang, Lei; Lemos, Henrique; Mautino, Mario R.; Mellor, Andrew L.

doi:10.3389/fimmu.2012.00109

Cited by 19 publications

(19 citation statements)

References 144 publications

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“…IDO mediates innate host defense to some pathogens by lowering the viability of pathogen-infected cells and increasing resistance of neighboring (uninfected) cells to pathogen infection [39], [40]. If IDO mediates host defense to influenza such functions were dispensable, as IDO ablation did not compromise overall host control of influenza infections.…”

Section: Discussionmentioning

confidence: 99%

Induction and Role of Indoleamine 2,3 Dioxygenase in Mouse Models of Influenza A Virus Infection

Huang

Klonowski

et al. 2013

PLoS ONE

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Influenza infection stimulates protective host immune responses but paradoxically enhances lung indoleamine 2,3 dioxygenase (IDO) activity, an enzyme that suppresses helper/effector T cells and activates Foxp3-lineage regulatory CD4 T cells (Tregs). Influenza A/PR/8/34 (PR8) infection stimulated rapid elevation of IDO activity in lungs and lung-draining mediastinal lymph nodes (msLNs). Mice lacking intact IDO1 genes (IDO1-KO mice) exhibited significantly lower morbidity after sub-lethal PR8 infection, and genetic or pharmacologic IDO ablation led to much faster recovery after virus clearance. More robust influenza-specific effector CD8 T cell responses manifested in lungs of PR8-infected IDO1-KO mice, though virus clearance rates were unaffected by IDO ablation. Similar outcomes manifested in mice infected with a less virulent influenza A strain (X31). IDO induction in X31-infected lungs was dependent on IFN type II (IFNγ) signaling and was restricted to non-hematopoietic cells, while redundant IFN type 1 or type II signaling induced IDO exclusively in hematopoietic cells from msLNs. Memory T cells generated in X31-primed IDO1-KO mice protected mice from subsequent challenge with lethal doses of PR8 (100×LD50). However recall T cell responses were less robust in lung interstitial tissues, and classic dominance of TCR Vβ8.3 chain usage amongst memory CD8+ T cells specific for influenza nucleoprotein (NP366) did not manifest in IDO1-KO mice. Thus, influenza induced IDO activity in lungs enhanced morbidity, slowed recovery, restrained effector T cell responses in lungs and shaped memory T cell repertoire generation, but did not attenuate virus clearance during primary influenza A infection.

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Section: Discussionmentioning

confidence: 99%

Induction and Role of Indoleamine 2,3 Dioxygenase in Mouse Models of Influenza A Virus Infection

Huang

Klonowski

et al. 2013

PLoS ONE

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“…Tryptophan, an essential amino acid, and its metabolites are suggested to be involved in the regulation of the immune system . Tryptophan is metabolized mainly through two different biosynthetic pathways: the generation of the neurotransmitter serotonin and the formation of kynurenine (KYN) derivatives .…”

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confidence: 99%

A tryptophan metabolite, kynurenine, promotes mast cell activation through aryl hydrocarbon receptor

Kawasaki

Chang

Tseng

et al. 2014

Allergy

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“…IDO1 encodes functional IDO protein that regulates T cell responses when expressed in some dendritic cells (Li et al, 2012). Depending on the context, IDO limits immune activator mechanisms, thus preventing a detrimental immune activity, or induces immunosuppression (Hainz et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Gene Expression of Indoleamine 2,3 Dioxygenase 1, Insulin-Growth Factor 1 and Red/IK Cytokine in Alopecia Areata

Şenilă¹,

Bălăcescu²,

Bălăcescu³

et al. 2014

Not Sci Biol

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Alopecia areata (AA) is a chronic, T-cell mediated autoimmune disease directed against the hair follicle, which partially evolves due to a loss of the immune privilege of the anagen hair follicle. The immune privilege is maintained by several factors, including a downregulation of MHC class I and II, local immunosupressants and expression of Fas ligand. The purpose of the study was to evaluate several factors involved in the collapse and restoration of the immune privilege. We investigated IDO1, IGF1 and red/IK gene expression in lesional and perilesionalscalp biopsies from alopecia areata patients. Seven paired punch-biopsies were taken from the active edge of alopecic plaque and from the perilesional scalp. Expression of IDO1, IGF1 and red/IK genes was performed by qRT-PCR. In lesional tissue, IGF1, IDO1 and red/IK genes showed an increase in the mRNA levels as compared with the perilesional scalp. By comparing the pairs of data for the investigated genes, IDO1was statistically upregulated in the lesional area. No significant differences were observed between the gene expression in mild or severe AA, from the lesional or perilesional areas.IDO1 mRNA expression was higher in patients with a relapse duration of less than 6 months as compared to patients with a relapse duration of more than 6 months; levels of IGF1 and red/IK mRNA are increased in lesionals compared to perilesional scalp area.

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Altered Tryptophan Metabolism as a Paradigm for Good and Bad Aspects of Immune Privilege in Chronic Inflammatory Diseases

Cited by 19 publications

References 144 publications

Induction and Role of Indoleamine 2,3 Dioxygenase in Mouse Models of Influenza A Virus Infection

Induction and Role of Indoleamine 2,3 Dioxygenase in Mouse Models of Influenza A Virus Infection

A tryptophan metabolite, kynurenine, promotes mast cell activation through aryl hydrocarbon receptor

Gene Expression of Indoleamine 2,3 Dioxygenase 1, Insulin-Growth Factor 1 and Red/IK Cytokine in Alopecia Areata

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