L-arginine metabolism in myeloid cells controls T-lymphocyte functions

Vincenzo Bronte, Paolo Serafini, Alessandra Mazzoni, David M. Segal, Paola Zanovello

Research output: Contribution to journalArticle

346 Citations (Scopus)

Abstract

Although current attention has focused on regulatory T lymphocytes as suppressors of autoimmune responses, powerful immunosuppression is also mediated by a subset of myeloid cells that enter the lymphoid organs and peripheral tissues during times of immune stress. If these myeloid suppressor cells (MSCs) receive signals from activated T lymphocytes in the lymphoid organs, they block T-cell proliferation. MSCs use two enzymes involved in arginine metabolism to control T-cell responses: inducible nitric oxide synthase (NOS2), which generates nitric oxide (NO) and arginase 1 (Arg1), which depletes the milieu of arginine. Th1 cytokines induce NOS2, whereas Th2 cytokines upregulate Arg1. Induction of either enzyme alone results in a reversible block in T-cell proliferation. When both enzymes are induced together, peroxynitrites, generated by NOS2 under conditions of limiting arginine, cause activated T lymphocytes to undergo apoptosis. Thus, NOS2 and Arg1 might act separately or synergistically in vivo to control specific types of T-cell responses, and selective antagonists of these enzymes might prove beneficial in fighting diseases in which T-cell responses are inappropriately suppressed. This Opinion is the second in a series on the regulation of the immune system by metabolic pathways.

Original languageEnglish
Pages (from-to)301-305
Number of pages5
JournalTrends in Immunology
Volume24
Issue number6
DOIs
StatePublished - Jun 1 2003
Externally publishedYes

Fingerprint

Myeloid Cells
Arginine
T-Lymphocytes
Arginase
Enzymes
Cell Proliferation
Cytokines
Enzyme Induction
Peroxynitrous Acid
Nitric Oxide Synthase Type II
Regulatory T-Lymphocytes
Metabolic Networks and Pathways
Autoimmunity
Immunosuppression
Immune System
Nitric Oxide
Up-Regulation
Referral and Consultation
Apoptosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

L-arginine metabolism in myeloid cells controls T-lymphocyte functions. / Bronte, Vincenzo; Serafini, Paolo; Mazzoni, Alessandra; Segal, David M.; Zanovello, Paola.

In: Trends in Immunology, Vol. 24, No. 6, 01.06.2003, p. 301-305.

Research output: Contribution to journalArticle

Bronte, Vincenzo ; Serafini, Paolo ; Mazzoni, Alessandra ; Segal, David M. ; Zanovello, Paola. / L-arginine metabolism in myeloid cells controls T-lymphocyte functions. In: Trends in Immunology. 2003 ; Vol. 24, No. 6. pp. 301-305.
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