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System A amino acid transporters regulate glutamine uptake and attenuate antibody-mediated arthritis.

Raposo, Bruno; Vaartjes, Daniëlle; Ahlqvist, Emma LU ; Nandakumar, Kutty-Selva and Holmdahl, Rikard (2015) In Immunology 146(4). p.607-617
Abstract
Proliferation of rapidly dividing bone marrow-derived cells is strongly dependent on the availability of free glutamine, whose uptake is mediated through different amino acid transporters. The sodium-coupled neutral amino acid transporter (SNAT) family was previously reported to be associated with the development of collagen-induced arthritis in mice. Here, we tested the hypothesis whether impairment of SNAT proteins influences immune cell function and in turn alters arthritis development. The 2-(methylamino)isobutyric acid (MeAIB), a SNAT-specific substrate, was used to modulate the function of SNAT proteins. We demonstrate that glutamine uptake by murine naïve lymphocytes, and consequent cell proliferation is strongly associated with... (More)
Proliferation of rapidly dividing bone marrow-derived cells is strongly dependent on the availability of free glutamine, whose uptake is mediated through different amino acid transporters. The sodium-coupled neutral amino acid transporter (SNAT) family was previously reported to be associated with the development of collagen-induced arthritis in mice. Here, we tested the hypothesis whether impairment of SNAT proteins influences immune cell function and in turn alters arthritis development. The 2-(methylamino)isobutyric acid (MeAIB), a SNAT-specific substrate, was used to modulate the function of SNAT proteins. We demonstrate that glutamine uptake by murine naïve lymphocytes, and consequent cell proliferation is strongly associated with system A transporters. Physiological impairment of SNAT proteins reduced antibody-initiated effector phase of arthritis, mainly by affecting the levels of circulating monocytes and neutrophils. MeAIB was also shown to affect the proliferation of immortalized cells, via trans-inhibition of SNAT proteins. Based on our observations, we conclude that SNAT proteins regulate the initial stages of lymphocyte activation by regulating glutamine uptake, and that the effector phase of arthritis can be affected by non-metabolized SNAT substrates. Most likely, metabolically active cells both within the adaptive and the innate immune system are regulated by SNAT proteins and play a role in modifying arthritis development. This article is protected by copyright. All rights reserved. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Immunology
volume
146
issue
4
pages
607 - 617
publisher
Wiley-Blackwell
external identifiers
  • pmid:26346312
  • wos:000368349600010
  • scopus:84954424736
ISSN
0019-2805
DOI
10.1111/imm.12531
language
English
LU publication?
yes
id
abf65380-2961-4a63-aca1-185fe811797f (old id 8042935)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26346312?dopt=Abstract
date added to LUP
2015-10-04 16:40:44
date last changed
2017-04-09 03:07:06
@article{abf65380-2961-4a63-aca1-185fe811797f,
  abstract     = {Proliferation of rapidly dividing bone marrow-derived cells is strongly dependent on the availability of free glutamine, whose uptake is mediated through different amino acid transporters. The sodium-coupled neutral amino acid transporter (SNAT) family was previously reported to be associated with the development of collagen-induced arthritis in mice. Here, we tested the hypothesis whether impairment of SNAT proteins influences immune cell function and in turn alters arthritis development. The 2-(methylamino)isobutyric acid (MeAIB), a SNAT-specific substrate, was used to modulate the function of SNAT proteins. We demonstrate that glutamine uptake by murine naïve lymphocytes, and consequent cell proliferation is strongly associated with system A transporters. Physiological impairment of SNAT proteins reduced antibody-initiated effector phase of arthritis, mainly by affecting the levels of circulating monocytes and neutrophils. MeAIB was also shown to affect the proliferation of immortalized cells, via trans-inhibition of SNAT proteins. Based on our observations, we conclude that SNAT proteins regulate the initial stages of lymphocyte activation by regulating glutamine uptake, and that the effector phase of arthritis can be affected by non-metabolized SNAT substrates. Most likely, metabolically active cells both within the adaptive and the innate immune system are regulated by SNAT proteins and play a role in modifying arthritis development. This article is protected by copyright. All rights reserved.},
  author       = {Raposo, Bruno and Vaartjes, Daniëlle and Ahlqvist, Emma and Nandakumar, Kutty-Selva and Holmdahl, Rikard},
  issn         = {0019-2805},
  language     = {eng},
  number       = {4},
  pages        = {607--617},
  publisher    = {Wiley-Blackwell},
  series       = {Immunology},
  title        = {System A amino acid transporters regulate glutamine uptake and attenuate antibody-mediated arthritis.},
  url          = {http://dx.doi.org/10.1111/imm.12531},
  volume       = {146},
  year         = {2015},
}