Open AccessTryptophan and arginine catabolic enzymes and regulatory cytokines in clinically isolated syndrome and multiple sclerosis
Author(s) -
Cha Lilian,
Jones Anderson P,
Trend Stephanie,
Byrne Scott N,
FabisPedrini Marzena J,
Carroll William M,
Lucas Robyn M,
Cole Judith M,
Booth David R,
Kermode Allan G,
Hart Prue H
Publication year - 2018
Publication title -
clinical and translational immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.321
H-Index - 34
ISSN - 2050-0068
DOI - 10.1002/cti2.1037
Subject(s) - immune system , peripheral blood mononuclear cell , arginase , ex vivo , cytokine , t cell , proinflammatory cytokine , regulatory t cell , immunology , indoleamine 2,3 dioxygenase , inflammation , homeostasis , biology , endocrinology , arginine , medicine , in vitro , il 2 receptor , tryptophan , biochemistry , amino acid
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 IDO 2 and arginase ( ARG ) 1 and ARG 2, respectively, was compared between peripheral blood mononuclear cells ( PBMC s) 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, PBMC s 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 IDO 1 expression, and TGFB mRNA levels correlated with ARG 1 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.