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System A amino acid...
System A amino acid transporters regulate glutamine uptake and attenuate antibody-mediated arthritis
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- Raposo, Bruno (författare)
- Karolinska Institutet
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- Vaartjes, Daniëlle (författare)
- Karolinska Institutet
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- Ahlqvist, Emma (författare)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,University Hospital of Malmö, Malmö, Sweden
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- Nandakumar, Kutty Selva, 1965- (författare)
- Karolinska Institutet
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- Holmdahl, Rikard (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2015-10-05
- 2015
- Engelska.
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Ingår i: Immunology. - Chichester : Wiley-Blackwell Publishing Inc.. - 0019-2805 .- 1365-2567. ; 146:4, s. 607-617
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Abstract
Ämnesord
Stäng
- 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 naive lymphocytes, and consequent cell proliferation, is strongly associated with system A transporters. Physiological impairment of SNAT proteins reduced the 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, through 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 probably, metabolically active cells within both the adaptive and the innate immune systems are regulated by SNAT proteins and play a role in modifying arthritis development. © 2015 John Wiley & Sons Ltd.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Nyckelord
- 2-(methylamino)isobutyric acid
- Amino acid transporter
- Arthritis
- Glutamine
- Sodium-coupled neutral amino acid transporter
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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