LIVIVO - Search results -

Search results

Result 1 - 10 of total 29

Search options

Article ; Online: Impact of IDO1 and IDO2 on the B Cell Immune Response.

Merlo, Lauren M F / Peng, Weidan / Mandik-Nayak, Laura

2022 Volume 13, Page(s) 886225

Abstract: Indoleamine-2,3-dioxygenase (IDO)1 and IDO2 are closely related tryptophan catabolizing enzymes that have immunomodulatory properties. Although initially studied as modifiers of T cell activity, emerging evidence suggests IDO1 and IDO2 also have ... ...

Abstract	Indoleamine-2,3-dioxygenase (IDO)1 and IDO2 are closely related tryptophan catabolizing enzymes that have immunomodulatory properties. Although initially studied as modifiers of T cell activity, emerging evidence suggests IDO1 and IDO2 also have important roles as modulators of B cell function. In this context, IDO1 and IDO2 appear to play opposite roles, with IDO1 inhibiting and IDO2 driving inflammatory B cell responses. In this mini review, we discuss the evidence for IDO1 and IDO2 modulation of B cell function, focusing on the effect of these enzymes on autoimmunity, allergic responses, protective immunity, and response to pathogens. We summarize strategies to target IDO1 and/or IDO2 as potential therapeutics for inflammatory autoimmune disease and highlight outstanding questions and areas that require future study.
MeSH term(s)	Immunity ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Tryptophan/pharmacology ; Tryptophan Oxygenase
Chemical Substances	Indoleamine-Pyrrole 2,3,-Dioxygenase ; Tryptophan (8DUH1N11BX) ; Tryptophan Oxygenase (EC 1.13.11.11)
Language	English
Publishing date	2022-04-13
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.886225
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: The Immunomodulatory Enzyme IDO2 Mediates Autoimmune Arthritis through a Nonenzymatic Mechanism.

Merlo, Lauren M F / Peng, Weidan / DuHadaway, James B / Montgomery, James D / Prendergast, George C / Muller, Alexander J / Mandik-Nayak, Laura

Journal of immunology (Baltimore, Md. : 1950)

2021 Volume 208, Issue 3, Page(s) 571–581

Abstract: IDO2 is one of two closely related tryptophan catabolizing enzymes induced under inflammatory conditions. In contrast to the immunoregulatory role defined for IDO1 in cancer models, IDO2 has a proinflammatory function in models of autoimmunity and ... ...

Abstract	IDO2 is one of two closely related tryptophan catabolizing enzymes induced under inflammatory conditions. In contrast to the immunoregulatory role defined for IDO1 in cancer models, IDO2 has a proinflammatory function in models of autoimmunity and contact hypersensitivity. In humans, two common single-nucleotide polymorphisms have been identified that severely impair IDO2 enzymatic function, such that <25% of individuals express IDO2 with full catalytic potential. This, together with IDO2's relatively weak enzymatic activity, suggests that IDO2 may have a role outside of its function in tryptophan catabolism. To determine whether the enzymatic activity of IDO2 is required for its proinflammatory function, we used newly generated catalytically inactive IDO2 knock-in mice together with established models of contact hypersensitivity and autoimmune arthritis. Contact hypersensitivity was attenuated in catalytically inactive IDO2 knock-in mice. In contrast, induction of autoimmune arthritis was unaffected by the absence of IDO2 enzymatic activity. In pursuing this nonenzymatic IDO2 function, we identified GAPDH, Runx1, RANbp10, and Mgea5 as IDO2-binding proteins that do not interact with IDO1, implicating them as potential mediators of IDO2-specific function. Taken together, our findings identify a novel function for IDO2, independent of its tryptophan catabolizing activity, and suggest that this nonenzymatic function could involve multiple signaling pathways. These data show that the enzymatic activity of IDO2 is required only for some inflammatory immune responses and provide, to our knowledge, the first evidence of a nonenzymatic role for IDO2 in mediating autoimmune disease.
MeSH term(s)	Animals ; Antigens, Neoplasm/metabolism ; Arthritis/immunology ; Autoimmunity/immunology ; Cell Line ; Core Binding Factor Alpha 2 Subunit/metabolism ; Gene Knock-In Techniques ; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)/metabolism ; Guanine Nucleotide Exchange Factors/metabolism ; HEK293 Cells ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Inflammation/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Microtubule-Associated Proteins/metabolism ; Polymorphism, Single Nucleotide/genetics
Chemical Substances	Antigens, Neoplasm ; Core Binding Factor Alpha 2 Subunit ; Guanine Nucleotide Exchange Factors ; IDO2 protein, mouse ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Microtubule-Associated Proteins ; RanBP10 protein, mouse ; Runx1 protein, mouse ; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) (EC 1.2.1.12)
Language	English
Publishing date	2021-12-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2100705
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ud II Zs.37: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 28: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: IDO2: A Pathogenic Mediator of Inflammatory Autoimmunity.

Merlo, Lauren M F / Mandik-Nayak, Laura

Clinical medicine insights. Pathology

2016 Volume 9, Issue Suppl 1, Page(s) 21–28

Abstract: Indoleamine 2,3-dioxygenase 2 (IDO2), a homolog of the better-studied tryptophan-catabolizing enzyme IDO1, is an immunomodulatory molecule with potential effects on various diseases including cancer and autoimmunity. Here, we review what is known about ... ...

Abstract	Indoleamine 2,3-dioxygenase 2 (IDO2), a homolog of the better-studied tryptophan-catabolizing enzyme IDO1, is an immunomodulatory molecule with potential effects on various diseases including cancer and autoimmunity. Here, we review what is known about the direct connections between IDO2 and immune function, particularly in relationship to autoimmune inflammatory disorders such as rheumatoid arthritis and lupus. Accumulating evidence indicates that IDO2 acts as a pro-inflammatory mediator of autoimmunity, with a functional phenotype distinct from IDO1. IDO2 is expressed in antigen-presenting cells, including B cells and dendritic cells, but affects inflammatory responses in the autoimmune context specifically by acting in B cells to modulate T cell help in multiple model systems. Given that expression of IDO2 can lead to exacerbation of inflammatory responses, IDO2 should be considered a potential therapeutic target for autoimmune disorders.
Language	English
Publishing date	2016-11-21
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	2578761-5
ISSN	1179-5557
ISSN	1179-5557
DOI	10.4137/CPath.S39930
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Application of simultaneous selective pressures slows adaptation.

Merlo, Lauren M F / Sprouffske, Kathleen / Howard, Taylor C / Gardiner, Kristin L / Caulin, Aleah F / Blum, Steven M / Evans, Perry / Bedalov, Antonio / Sniegowski, Paul D / Maley, Carlo C

Evolutionary applications

2020 Volume 13, Issue 7, Page(s) 1615–1625

Abstract: Beneficial mutations that arise in an evolving asexual population may compete or interact in ways that alter the overall rate of adaptation through mechanisms such as clonal or functional interference. The application of multiple selective pressures ... ...

Abstract	Beneficial mutations that arise in an evolving asexual population may compete or interact in ways that alter the overall rate of adaptation through mechanisms such as clonal or functional interference. The application of multiple selective pressures simultaneously may allow for a greater number of adaptive mutations, increasing the opportunities for competition between selectively advantageous alterations, and thereby reducing the rate of adaptation. We evolved a strain of
Language	English
Publishing date	2020-08-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2405496-3
ISSN	1752-4563 ; 1752-4571
ISSN (online)	1752-4563
ISSN	1752-4571
DOI	10.1111/eva.13062
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Differential Roles of IDO1 and IDO2 in T and B Cell Inflammatory Immune Responses.

Merlo, Lauren M F / DuHadaway, James B / Montgomery, James D / Peng, Wei-Dan / Murray, Peter J / Prendergast, George C / Caton, Andrew J / Muller, Alexander J / Mandik-Nayak, Laura

Frontiers in immunology

2020 Volume 11, Page(s) 1861

Abstract: Indoleamine-2,3-dioxygenase (IDO)1 and IDO2 are two closely related tryptophan catabolizing enzymes encoded by linked genes. The IDO pathway is also immunomodulatory, with IDO1 well-characterized as a mediator of tumor immune evasion. Due to its homology ...

Abstract	Indoleamine-2,3-dioxygenase (IDO)1 and IDO2 are two closely related tryptophan catabolizing enzymes encoded by linked genes. The IDO pathway is also immunomodulatory, with IDO1 well-characterized as a mediator of tumor immune evasion. Due to its homology with IDO1, IDO2 has been proposed to have a similar immunoregulatory function. Indeed, IDO2, like IDO1, is necessary for the differentiation of regulatory T cells
MeSH term(s)	Animals ; Arthritis, Experimental/immunology ; B-Lymphocytes/immunology ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/immunology ; Inflammation/immunology ; Lymphocyte Activation/immunology ; Mice ; Mice, Knockout ; Orthomyxoviridae Infections/immunology ; T-Lymphocytes/immunology
Chemical Substances	IDO1 protein, mouse ; IDO2 protein, mouse ; Indoleamine-Pyrrole 2,3,-Dioxygenase
Language	English
Publishing date	2020-08-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.01861
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: IDO2 is critical for IDO1-mediated T-cell regulation and exerts a non-redundant function in inflammation.

Metz, Richard / Smith, Courtney / DuHadaway, James B / Chandler, Phillip / Baban, Babak / Merlo, Lauren M F / Pigott, Elizabeth / Keough, Martin P / Rust, Sonja / Mellor, Andrew L / Mandik-Nayak, Laura / Muller, Alexander J / Prendergast, George C

International immunology

2019 Volume 31, Issue 3, Page(s) 181–182

Language	English
Publishing date	2019-06-19
Publishing country	England
Document type	Journal Article ; Published Erratum
ZDB-ID	1013745-2
ISSN	1460-2377 ; 0953-8178
ISSN (online)	1460-2377
ISSN	0953-8178
DOI	10.1093/intimm/dxz003
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2619: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 70: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The role of genetic diversity in cancer.

Merlo, Lauren M F / Maley, Carlo C

The Journal of clinical investigation

2010 Volume 120, Issue 2, Page(s) 401–403

Abstract: The role of genetic heterogeneity within neoplasms is increasingly recognized as important for understanding the dynamics of cancer progression, cancer stem cells, and therapeutic resistance, and there is interest in intratumoral heterogeneity ... ...

Abstract	The role of genetic heterogeneity within neoplasms is increasingly recognized as important for understanding the dynamics of cancer progression, cancer stem cells, and therapeutic resistance, and there is interest in intratumoral heterogeneity measurements as potential biomarkers for risk stratification. In this issue of the JCI, Park et al. characterize this genetic diversity in carcinoma in situ and in invasive regions from 3 types of human breast cancers and lay the groundwork for translation of these measures to the clinic.
MeSH term(s)	Breast Neoplasms/genetics ; Carcinoma in Situ/genetics ; Disease Progression ; Female ; Genetic Variation ; Humans ; Incidence ; Neoplasms/epidemiology ; Neoplasms/genetics ; Neoplasms/pathology ; Neoplastic Stem Cells/pathology ; Precancerous Conditions/genetics
Language	English
Publishing date	2010-01-25
Publishing country	United States
Document type	Comment ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI42088
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ua VI Zs.184: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Peptide vaccination directed against IDO1-expressing immune cells elicits CD8

Dey, Souvik / Sutanto-Ward, Erika / Kopp, Katharina L / DuHadaway, James / Mondal, Arpita / Ghaban, Dema / Lecoq, Inés / Zocca, Mai-Britt / Merlo, Lauren M F / Mandik-Nayak, Laura / Andersen, Mads Hald / Pedersen, Ayako Wakatsuki / Muller, Alexander J

Journal for immunotherapy of cancer

2020 Volume 8, Issue 2

Abstract: Background: The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which subverts T-cell immunity at multiple levels, is itself subject to inherent T-cell reactivity. This intriguing deviation from central tolerance has been ... ...

Abstract	Background: The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which subverts T-cell immunity at multiple levels, is itself subject to inherent T-cell reactivity. This intriguing deviation from central tolerance has been interpreted as counterbalancing IDO1-mediated immunosuppression. Based on this hypothesis, clinical studies employing an IDO1 peptide-based vaccine approach for cancer treatment have been initiated, but there remains a pressing need to further investigate the immunological ramifications of stimulating the anti-IDO1 T-cell response in this manner. Methods: CT26 colon carcinoma tumors were evaluated for expression of IDO1 protein by western blot analysis, immunofluorescence microscopy and flow cytometry. Mouse IDO1-derived peptides, predicted to bind either major histocompatibility complex (MHC) class I or II of the H2 Results: This study identifies mouse MHC class I-directed and II-directed, IDO1-derived peptides capable of eliciting antitumor responses, despite finding IDO1 expressed exclusively in tumor-infiltrating immune cells. Treatment of established tumors with anti-PD1 antibody and class I-directed but not class II-directed IDO1 peptide vaccines produced an enhanced antitumor response. Likewise, class I-directed and II-directed IDO1 peptides elicited an enhanced combinatorial response, suggesting distinct mechanisms of action. Consistent with this interpretation, adoptive transfer of isolated CD8 Conclusions: The in vivo antitumor effects demonstrated with IDO1-based vaccines via targeting of the tumor microenvironment highlight the utility of mouse models for further exploration and refinement of this novel vaccine-based approach to IDO1-directed cancer therapy and its potential to improve patient response rates to anti-PD1 therapy.
Language	English
Publishing date	2020-06-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2020-000605
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: IDO2 in Immunomodulation and Autoimmune Disease.

Prendergast, George C / Metz, Richard / Muller, Alexander J / Merlo, Lauren M F / Mandik-Nayak, Laura

Frontiers in immunology

2014 Volume 5, Page(s) 585

Abstract: IDO2 is a relative of IDO1 implicated in tryptophan catabolism and immune modulation but its specific contributions to normal physiology and pathophysiology are not known. Evolutionary genetic studies suggest that IDO2 has a unique function ancestral to ... ...

Abstract	IDO2 is a relative of IDO1 implicated in tryptophan catabolism and immune modulation but its specific contributions to normal physiology and pathophysiology are not known. Evolutionary genetic studies suggest that IDO2 has a unique function ancestral to IDO1. In mice, IDO2 gene deletion does not appreciably affect embryonic development or hematopoiesis, but it leads to defects in allergic or autoimmune responses and in the ability of IDO1 to influence the generation of T regulatory cells. Gene expression studies indicate that IDO2 is a basally and more narrowly expressed gene than IDO1 and that IDO2 is uniquely regulated by AhR, which serves as a physiological receptor for the tryptophan catabolite kynurenine. In the established KRN transgenic mouse model of rheumatoid arthritis, where IDO1 gene deletion has no effect, IDO2 deletion selectively blunts responses to autoantigen but has no effect on responses to neoantigen challenge. In human populations, natural variations in IDO2 gene sequence that attenuate enzymatic activity have been reported to influence brain cancer control and adaptive immune responses to the IDO2 protein itself, consistent with the concept that IDO2 is involved in shaping immune tolerance in human beings. Biochemical and pharmacological studies provide further evidence of differences in IDO2 enzymology and function relative to IDO1. We suggest that IDO2 may act in a distinct manner from IDO1 as a set-point for tolerance to "altered-self" antigens along the self-non-self continuum where immune challenges from cancer and autoimmunity may arise.
Language	English
Publishing date	2014
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2014.00585
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

Order via subito

Details ▾
- Full text online
- Order with fees

Article ; Online: IDO2 Modulates T Cell-Dependent Autoimmune Responses through a B Cell-Intrinsic Mechanism.

Merlo, Lauren M F / DuHadaway, James B / Grabler, Samantha / Prendergast, George C / Muller, Alexander J / Mandik-Nayak, Laura

Journal of immunology (Baltimore, Md. : 1950)

2016 Volume 196, Issue 11, Page(s) 4487–4497

Abstract: Mechanistic insight into how adaptive immune responses are modified along the self-nonself continuum may offer more effective opportunities to treat autoimmune disease, cancer, and other sterile inflammatory disorders. Recent genetic studies in the KRN ... ...

Abstract	Mechanistic insight into how adaptive immune responses are modified along the self-nonself continuum may offer more effective opportunities to treat autoimmune disease, cancer, and other sterile inflammatory disorders. Recent genetic studies in the KRN mouse model of rheumatoid arthritis demonstrate that the immunomodulatory molecule IDO2 modifies responses to self-antigens; however, the mechanisms involved are obscure. In this study, we show that IDO2 exerts a critical function in B cells to support the generation of autoimmunity. In experiments with IDO2-deficient mice, adoptive transplant experiments demonstrated that IDO2 expression in B cells was both necessary and sufficient to support robust arthritis development. IDO2 function in B cells was contingent on a cognate, Ag-specific interaction to exert its immunomodulatory effects on arthritis development. We confirmed a similar requirement in an established model of contact hypersensitivity, in which IDO2-expressing B cells are required for a robust inflammatory response. Mechanistic investigations showed that IDO2-deficient B cells lacked the ability to upregulate the costimulatory marker CD40, suggesting IDO2 acts at the T-B cell interface to modulate the potency of T cell help needed to promote autoantibody production. Overall, our findings revealed that IDO2 expression by B cells modulates autoimmune responses by supporting the cross talk between autoreactive T and B cells.
MeSH term(s)	Animals ; Autoimmunity/immunology ; B-Lymphocytes/immunology ; Cells, Cultured ; Indoleamine-Pyrrole 2,3,-Dioxygenase/deficiency ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics ; Indoleamine-Pyrrole 2,3,-Dioxygenase/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; T-Lymphocytes/immunology
Chemical Substances	IDO2 protein, mouse ; Indoleamine-Pyrrole 2,3,-Dioxygenase
Language	English
Publishing date	2016-06-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1600141
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ud II Zs.37: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 28: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito