Tryptophan and arginine catabolic enzymes and regulatory cytokines in clinically isolated syndrome and multiple sclerosis

Lilian Cha, Anderson P. Jones, Stephanie Trend, Scott N. Byrne, Marzena J. Fabis-Pedrini, William M. Carroll, Robyn M. Lucas, Judith M. Cole, David R. Booth, Allan G. Kermode, Prue H. Hart

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objectives: Clinically isolated syndrome (CIS) is the earliest clinical episode in multiple sclerosis (MS). A study of circulating cells from patients with CIS may help us understand the transition to, and processes associated with, the development of MS. Methods: As immune cell activity can be determined by flux through metabolic pathways, the mRNA expression of l-tryptophan- and l-arginine-catabolising enzymes, indoleamine 2,3-dioxygenase (IDO) 1 and IDO2 and arginase (ARG) 1 and ARG2, respectively, was compared between peripheral blood mononuclear cells (PBMCs) from healthy controls, and patients with CIS and definite MS. As one measure of cell function, cytokine mRNA levels were analysed directly ex vivo and in cells after culture for 4 h in the absence of regulatory factors in autologous serum. Results: When measured directly ex vivo, the expression of IDO and ARG was greater in cells from patients with CIS and MS than cells from healthy controls. Although not linked to IDO and ARG expression, PBMCs from the CIS patients were characterised by low IL-10 and TGFB mRNA levels and not by greater expression of proinflammatory cytokines. When the cells were cultured for 4 h without autologous serum, pro- and anti-inflammatory cytokine mRNA levels positively correlated with IDO1 expression, and TGFB mRNA levels correlated with ARG1 expression. Conclusion: Higher IDO and ARG expression in CIS and MS provides one sustained homeostatic mechanism to control MS-associated inflammation. However, potent extrinsic mediators in serum may regulate immune cell function in CIS and associations between IDO, ARG and cytokine expression.

Original languageEnglish
Article numbere1037
JournalClinical and Translational Immunology
Volume7
Issue number8
DOIs
Publication statusPublished - 1 Jan 2018

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Tryptophan
Arginase
Multiple Sclerosis
Arginine
Cytokines
Enzymes
Messenger RNA
Blood Cells
Serum
Metabolic Networks and Pathways
Interleukin-10
Cultured Cells
Anti-Inflammatory Agents
Cell Culture Techniques
Inflammation

Cite this

Cha, Lilian ; Jones, Anderson P. ; Trend, Stephanie ; Byrne, Scott N. ; Fabis-Pedrini, Marzena J. ; Carroll, William M. ; Lucas, Robyn M. ; Cole, Judith M. ; Booth, David R. ; Kermode, Allan G. ; Hart, Prue H. / Tryptophan and arginine catabolic enzymes and regulatory cytokines in clinically isolated syndrome and multiple sclerosis. In: Clinical and Translational Immunology. 2018 ; Vol. 7, No. 8.
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title = "Tryptophan and arginine catabolic enzymes and regulatory cytokines in clinically isolated syndrome and multiple sclerosis",
abstract = "Objectives: Clinically isolated syndrome (CIS) is the earliest clinical episode in multiple sclerosis (MS). A study of circulating cells from patients with CIS may help us understand the transition to, and processes associated with, the development of MS. Methods: As immune cell activity can be determined by flux through metabolic pathways, the mRNA expression of l-tryptophan- and l-arginine-catabolising enzymes, indoleamine 2,3-dioxygenase (IDO) 1 and IDO2 and arginase (ARG) 1 and ARG2, respectively, was compared between peripheral blood mononuclear cells (PBMCs) from healthy controls, and patients with CIS and definite MS. As one measure of cell function, cytokine mRNA levels were analysed directly ex vivo and in cells after culture for 4 h in the absence of regulatory factors in autologous serum. Results: When measured directly ex vivo, the expression of IDO and ARG was greater in cells from patients with CIS and MS than cells from healthy controls. Although not linked to IDO and ARG expression, PBMCs from the CIS patients were characterised by low IL-10 and TGFB mRNA levels and not by greater expression of proinflammatory cytokines. When the cells were cultured for 4 h without autologous serum, pro- and anti-inflammatory cytokine mRNA levels positively correlated with IDO1 expression, and TGFB mRNA levels correlated with ARG1 expression. Conclusion: Higher IDO and ARG expression in CIS and MS provides one sustained homeostatic mechanism to control MS-associated inflammation. However, potent extrinsic mediators in serum may regulate immune cell function in CIS and associations between IDO, ARG and cytokine expression.",
keywords = "3-dioxygenase, arginase, clinically isolated syndrome, cytokines, indoleamine 2, multiple sclerosis, peripheral blood mononuclear cells",
author = "Lilian Cha and Jones, {Anderson P.} and Stephanie Trend and Byrne, {Scott N.} and Fabis-Pedrini, {Marzena J.} and Carroll, {William M.} and Lucas, {Robyn M.} and Cole, {Judith M.} and Booth, {David R.} and Kermode, {Allan G.} and Hart, {Prue H.}",
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Tryptophan and arginine catabolic enzymes and regulatory cytokines in clinically isolated syndrome and multiple sclerosis. / Cha, Lilian; Jones, Anderson P.; Trend, Stephanie; Byrne, Scott N.; Fabis-Pedrini, Marzena J.; Carroll, William M.; Lucas, Robyn M.; Cole, Judith M.; Booth, David R.; Kermode, Allan G.; Hart, Prue H.

In: Clinical and Translational Immunology, Vol. 7, No. 8, e1037, 01.01.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Tryptophan and arginine catabolic enzymes and regulatory cytokines in clinically isolated syndrome and multiple sclerosis

AU - Cha, Lilian

AU - Jones, Anderson P.

AU - Trend, Stephanie

AU - Byrne, Scott N.

AU - Fabis-Pedrini, Marzena J.

AU - Carroll, William M.

AU - Lucas, Robyn M.

AU - Cole, Judith M.

AU - Booth, David R.

AU - Kermode, Allan G.

AU - Hart, Prue H.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objectives: Clinically isolated syndrome (CIS) is the earliest clinical episode in multiple sclerosis (MS). A study of circulating cells from patients with CIS may help us understand the transition to, and processes associated with, the development of MS. Methods: As immune cell activity can be determined by flux through metabolic pathways, the mRNA expression of l-tryptophan- and l-arginine-catabolising enzymes, indoleamine 2,3-dioxygenase (IDO) 1 and IDO2 and arginase (ARG) 1 and ARG2, respectively, was compared between peripheral blood mononuclear cells (PBMCs) from healthy controls, and patients with CIS and definite MS. As one measure of cell function, cytokine mRNA levels were analysed directly ex vivo and in cells after culture for 4 h in the absence of regulatory factors in autologous serum. Results: When measured directly ex vivo, the expression of IDO and ARG was greater in cells from patients with CIS and MS than cells from healthy controls. Although not linked to IDO and ARG expression, PBMCs from the CIS patients were characterised by low IL-10 and TGFB mRNA levels and not by greater expression of proinflammatory cytokines. When the cells were cultured for 4 h without autologous serum, pro- and anti-inflammatory cytokine mRNA levels positively correlated with IDO1 expression, and TGFB mRNA levels correlated with ARG1 expression. Conclusion: Higher IDO and ARG expression in CIS and MS provides one sustained homeostatic mechanism to control MS-associated inflammation. However, potent extrinsic mediators in serum may regulate immune cell function in CIS and associations between IDO, ARG and cytokine expression.

AB - Objectives: Clinically isolated syndrome (CIS) is the earliest clinical episode in multiple sclerosis (MS). A study of circulating cells from patients with CIS may help us understand the transition to, and processes associated with, the development of MS. Methods: As immune cell activity can be determined by flux through metabolic pathways, the mRNA expression of l-tryptophan- and l-arginine-catabolising enzymes, indoleamine 2,3-dioxygenase (IDO) 1 and IDO2 and arginase (ARG) 1 and ARG2, respectively, was compared between peripheral blood mononuclear cells (PBMCs) from healthy controls, and patients with CIS and definite MS. As one measure of cell function, cytokine mRNA levels were analysed directly ex vivo and in cells after culture for 4 h in the absence of regulatory factors in autologous serum. Results: When measured directly ex vivo, the expression of IDO and ARG was greater in cells from patients with CIS and MS than cells from healthy controls. Although not linked to IDO and ARG expression, PBMCs from the CIS patients were characterised by low IL-10 and TGFB mRNA levels and not by greater expression of proinflammatory cytokines. When the cells were cultured for 4 h without autologous serum, pro- and anti-inflammatory cytokine mRNA levels positively correlated with IDO1 expression, and TGFB mRNA levels correlated with ARG1 expression. Conclusion: Higher IDO and ARG expression in CIS and MS provides one sustained homeostatic mechanism to control MS-associated inflammation. However, potent extrinsic mediators in serum may regulate immune cell function in CIS and associations between IDO, ARG and cytokine expression.

KW - 3-dioxygenase

KW - arginase

KW - clinically isolated syndrome

KW - cytokines

KW - indoleamine 2

KW - multiple sclerosis

KW - peripheral blood mononuclear cells

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