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Origin and Function of Tryptophan Metabolites Modulating CD4 + T Cells in Lupus-Prone Mice

42 Pages Posted: 14 Dec 2021 Publication Status: Published

See all articles by Josephine Brown

Josephine Brown

University of Florida

Georges Abboud

University of Florida

Seung-Chul Choi

University of Florida

Longhuan Ma

University of Florida

Nathalie Kanda

University of Florida

Leilani Zeumer-Spataro

University of Florida

Jean Lee

University of Chicago

Weidan Peng

Lankenau Institute for Medical Research

Joy Cagmat

University of Florida

Tamas Faludi

Lankenau Institute for Medical Research

Mansour Mohamadzadeh

University of Texas Health San Antonio

Timothy Garrett

University of Florida - Department of Pathology, Immunology, and Laboratory Medicine

Laura Mandik-Nayak

Lankenau Institute for Medical Research

Alexander Chervonsky

University of Chicago

Andras Perl

State University of New York (SUNY) - SUNY Upstate Medical University

Laurence Morel

University of Florida

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Abstract

SUMMARYA skewed tryptophan metabolism has been reported in lupus patients. Here, we investigated the mechanisms by which it occurs in lupus-susceptible mice, and how tryptophan metabolites exacerbate T cell activation. Metabolomic analyses demonstrated that tryptophan is differentially catabolized in lupus mice compared to controls and that the microbiota played a role in this skewing. There was no evidence for differential expression of tryptophan catabolic enzymes in lupus mice, further supporting a major contribution of the microbiota to skewing. However, isolated lupus T cells processed tryptophan differently, suggesting a contribution of T cell intrinsic factors. Functionally, tryptophan and its microbial product tryptamine increased T cell metabolism and mTOR activation, while kynurenine promoted interferon gamma production, all of which have been associated with lupus. These results showed that a combination of microbial and T-cell intrinsic factors promote the production of tryptophan metabolites that enhance inflammatory phenotypes in lupus T cells.

Suggested Citation

Brown, Josephine and Abboud, Georges and Choi, Seung-Chul and Ma, Longhuan and Kanda, Nathalie and Zeumer-Spataro, Leilani and Lee, Jean and Peng, Weidan and Cagmat, Joy and Faludi, Tamas and Mohamadzadeh, Mansour and Garrett, Timothy and Mandik-Nayak, Laura and Chervonsky, Alexander and Perl, Andras and Morel, Laurence, Origin and Function of Tryptophan Metabolites Modulating CD4 + T Cells in Lupus-Prone Mice. Available at SSRN: https://ssrn.com/abstract=3985175 or http://dx.doi.org/10.2139/ssrn.3985175
This version of the paper has not been formally peer reviewed.

Josephine Brown

University of Florida ( email )

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

Georges Abboud

University of Florida ( email )

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

Seung-Chul Choi

University of Florida ( email )

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

Longhuan Ma

University of Florida ( email )

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

Nathalie Kanda

University of Florida ( email )

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

Leilani Zeumer-Spataro

University of Florida ( email )

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

Jean Lee

University of Chicago ( email )

1101 East 58th Street
Chicago, IL 60637
United States

Weidan Peng

Lankenau Institute for Medical Research ( email )

United States

Joy Cagmat

University of Florida ( email )

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

Tamas Faludi

Lankenau Institute for Medical Research ( email )

United States

Mansour Mohamadzadeh

University of Texas Health San Antonio ( email )

United States

Timothy Garrett

University of Florida - Department of Pathology, Immunology, and Laboratory Medicine

Laura Mandik-Nayak

Lankenau Institute for Medical Research ( email )

United States

Alexander Chervonsky

University of Chicago ( email )

1101 East 58th Street
Chicago, IL 60637
United States

Andras Perl

State University of New York (SUNY) - SUNY Upstate Medical University ( email )

College of Health Professions
Department of Physical Therapy
Syracuse, NY 13210
United States

Laurence Morel (Contact Author)

University of Florida ( email )

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

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