Nature Search

Metabotropic glutamate receptor-4 modulates adaptive immunity and restrains neuroinflammation

Excessive glutamate seen in multiple sclerosis leads to excitotoxicity and neuronal dysfunction. Fallarino et al. find that the clinical signs and neuroinflammation in experimental autoimmune encephalitis is worsened in mice deficient in the metabotropic glutamate receptor-4. Small molecules that enhance signaling through this receptor suppress neuroinflammation by promoting T regulatory cell development and suppressing T_H17 responses. This cross-talk between the nervous and immune system suggests an endogenous mechanism to suppress neuroinflammation in the context of multiple sclerosis.

Francesca Fallarino
Claudia Volpi
Roberto Di Marco
Research25 Jul 2010
Nature Medicine

Volume: 16, P: 897-902
A microbially produced AhR ligand promotes a Tph1-driven tolerogenic program in multiple sclerosis

Teresa Zelante
Giuseppe Paolicelli
Luigina Romani
ResearchOpen Access20 Mar 2024
Scientific Reports

Volume: 14, P: 1-16
CTLA-4–Ig regulates tryptophan catabolism in vivo

Ursula Grohmann
Ciriana Orabona
Paolo Puccetti
Research30 Sept 2002
Nature Immunology

Volume: 3, P: 1097-1101
Impact of liver fibrosis on AAV-mediated gene transfer to mouse hepatocytes

Ferriero et al. show that liver fibrosis reduces the efficiency of AAV-based gene therapy by limiting liver uptake and altering vector distribution to other organs. The impact of fibrosis varies depending on the AAV variant, highlighting the need for tailored approaches in fibrotic diseases.

Rosa Ferriero
Gemma Bruno
Pasquale Piccolo
ResearchOpen Access10 Mar 2025
Nature Communications

Volume: 16, P: 1-13
Author Correction: Thymosin α1 represents a potential potent single-molecule-based therapy for cystic fibrosis

Luigina Romani
Vasilis Oikonomou
Enrico Garaci
Amendments and Corrections22 Jun 2018
Nature Medicine

Volume: 24, P: 1481
Publisher Correction: Thymosin α1 represents a potential potent single-molecule-based therapy for cystic fibrosis

Luigina Romani
Vasilis Oikonomou
Enrico Garaci
Amendments and Corrections22 Jun 2018
Nature Medicine

Volume: 24, P: 1482
Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells

The tryptophan-catalytic activity of IDO in dendritic cells is known to regulate immune responses. Grohmann and co-workers show that IDO also functions as an intracellular signal transducer in response to transforming growth factor-β.

Maria T Pallotta
Ciriana Orabona
Ursula Grohmann
Research31 Jul 2011
Nature Immunology

Volume: 12, P: 870-878
3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine

3-hydroxy-L-kynurenamine (3-HKA) is a metabolite deriving from a lateral pathway of tryptophan catabolism. Here the authors identify 3-HKA as a biogenic amine and show it has anti-inflammatory properties that can protect mice against psoriasis and nephrotoxic nephritis.

Cristina C. Clement
Angelo D’Alessandro
Laura Santambrogio
ResearchOpen Access21 Jul 2021
Nature Communications

Volume: 12, P: 1-17
Aryl hydrocarbon receptor control of a disease tolerance defence pathway

Initial exposure to lipopolysaccharide (LPS) induces endotoxin tolerance, which reduces immunological reactions to LPS; here it is shown that primary LPS challenge is controlled by AhR, TDO2 and IL-10, whereas sustained effects require AhR, IDO1 and TGF-β, allowing for disease tolerance with reduced immunopathology in infections.

Alban Bessede
Marco Gargaro
Paolo Puccetti
Research09 Jul 2014
Nature

Volume: 511, P: 184-190
CD28 induces immunostimulatory signals in dendritic cells via CD80 and CD86

Ciriana Orabona
Ursula Grohmann
Paolo Puccetti
Research03 Oct 2004
Nature Immunology

Volume: 5, P: 1134-1142
High doses of CpG oligodeoxynucleotides stimulate a tolerogenic TLR9–TRIF pathway

CpG oligodeoxynucleotides stimulate innate immune signalling and are of significant interest as therapeutics. Here the authors show that at high doses, these molecules induce an opposite, tolerogenic effect, acting through a previously uncharacterized Toll-like receptor-dependent pathway.

Claudia Volpi
Francesca Fallarino
Paolo Puccetti
Research14 May 2013
Nature Communications

Volume: 4, P: 1-11
Modulation of tryptophan catabolism by regulatory T cells

Francesca Fallarino
Ursula Grohmann
Paolo Puccetti
Research26 Oct 2003
Nature Immunology

Volume: 4, P: 1206-1212
BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1

Norihiko Watanabe
Maya Gavrieli
Kenneth M Murphy
Research08 Jun 2003
Nature Immunology

Volume: 4, P: 670-679
Reverse signaling through GITR ligand enables dexamethasone to activate IDO in allergy

Ursula Grohmann
Claudia Volpi
Paolo Puccetti
Research08 Apr 2007
Nature Medicine

Volume: 13, P: 579-586
Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration

Immunogenicity of AAV vectors renders repeated AAV dosing ineffective. Here the authors show that coadministration of nanoparticle-encapsulated rapamycin overcomes AAV immunogenicity through Treg induction, enabling efficient AAV redosing in mice and nonhuman primates.

Amine Meliani
Florence Boisgerault
Federico Mingozzi
ResearchOpen Access05 Oct 2018
Nature Communications

Volume: 9, P: 1-13
Thymosin α1 represents a potential potent single-molecule-based therapy for cystic fibrosis

Thymosin α1 is used in the clinic as a treatment in viral disease and acts as an anti-inflammatory. Here it was found to also correct the misfolding of mutant CTFR and potentiate its activity, thus improving outcome in a mouse model of cystic fibrosis.

Luigina Romani
Vasilis Oikonomou
Enrico Garaci
Research10 Apr 2017
Nature Medicine

Volume: 23, P: 590-600
Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease

Chronic granulomatous disease is associated with lack of NADPH activity in phagocytes and characterized by recurrent bacterial and fungal infections as well as exagerated inflammation. This paper shows that the excessive inflammation can be attributed to the lack of NAPPH-derived reactive oxygen which is required for the conversion of tryptophan to kynurenine.

Luigina Romani
Francesca Fallarino
Paolo Puccetti
Research10 Jan 2008
Nature

Volume: 451, P: 211-215
Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond

Imbalances in the kynurenine pathway (KP) of tryptophan metabolism are associated with CNS disorders, infectious diseases, autoimmune diseases and cancer, highlighting KP enzymes as potential therapeutic targets. Here, Platten and colleagues provide an overview of the physiological and pathophysiological roles of tryptophan metabolism, focusing on the clinical potential and challenges associated with targeting this pathway.

Michael Platten
Ellen A. A. Nollen
Christiane A. Opitz
Reviews13 Feb 2019
Nature Reviews Drug Discovery

Volume: 18, P: 379-401
HOPS/Tmub1 involvement in the NF-kB-mediated inflammatory response through the modulation of TRAF6

Marina Maria Bellet
Stefania Pieroni
Giuseppe Servillo
ResearchOpen Access15 Oct 2020
Cell Death & Disease

Volume: 11, P: 1-14
Effects of a nutraceutical combination on lipids, inflammation and endothelial integrity in patients with subclinical inflammation: a randomized clinical trial

Matteo Pirro
Massimo R. Mannarino
Elmo Mannarino
ResearchOpen Access23 Mar 2016
Scientific Reports

Volume: 6, P: 1-9

Search

Metabotropic glutamate receptor-4 modulates adaptive immunity and restrains neuroinflammation

A microbially produced AhR ligand promotes a Tph1-driven tolerogenic program in multiple sclerosis

CTLA-4–Ig regulates tryptophan catabolism in vivo

Impact of liver fibrosis on AAV-mediated gene transfer to mouse hepatocytes

Author Correction: Thymosin α1 represents a potential potent single-molecule-based therapy for cystic fibrosis

Publisher Correction: Thymosin α1 represents a potential potent single-molecule-based therapy for cystic fibrosis

Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells

3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine

Aryl hydrocarbon receptor control of a disease tolerance defence pathway

CD28 induces immunostimulatory signals in dendritic cells via CD80 and CD86

High doses of CpG oligodeoxynucleotides stimulate a tolerogenic TLR9–TRIF pathway

Modulation of tryptophan catabolism by regulatory T cells

BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1

Reverse signaling through GITR ligand enables dexamethasone to activate IDO in allergy

Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration

Thymosin α1 represents a potential potent single-molecule-based therapy for cystic fibrosis

Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease

Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond

HOPS/Tmub1 involvement in the NF-kB-mediated inflammatory response through the modulation of TRAF6

Effects of a nutraceutical combination on lipids, inflammation and endothelial integrity in patients with subclinical inflammation: a randomized clinical trial

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