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IL-2Rβγ signalling ...
IL-2Rβγ signalling in lymphocytes promotes systemic inflammation and reduces plasma cholesterol in atherosclerotic mice
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- Mulholland, Megan (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - cellulär metabolism och inflammation,Forskargrupper vid Lunds universitet,Cardiovascular Research - Cellular Metabolism and Inflammation,Lund University Research Groups,Skåne University Hospital
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- Jakobsson, Gabriel (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Skåne University Hospital
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- Lei, Yu (författare)
- Karolinska Institutet,Karolinska Institute
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- Sundius, Lena (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - translationella studier,Forskargrupper vid Lunds universitet,Cardiovascular Research - Translational Studies,Lund University Research Groups,Skåne University Hospital
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- Ljungcrantz, Irena (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Skåne University Hospital
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- Rattik, Sara (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - cellulär metabolism och inflammation,Forskargrupper vid Lunds universitet,Cardiovascular Research - Cellular Metabolism and Inflammation,Lund University Research Groups,Skåne University Hospital
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- Tietge, Uwe J F (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Engelbertsen, Daniel (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - cellulär metabolism och inflammation,Forskargrupper vid Lunds universitet,Cardiovascular Research - Cellular Metabolism and Inflammation,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- Engelska 10 s.
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 326, s. 1-10
- Relaterad länk:
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http://dx.doi.org/10... (free)
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http://www.atheroscl...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- BACKGROUND AND AIMS: The relationship between inflammation and lipid metabolism is complex and bidirectional. Lymphocyte-driven inflammation has been shown to modulate both atherosclerotic plaque development and cholesterol levels, but the mechanisms are incompletely understood.METHODS: The cardiometabolic effects of IL-2Rβγ signalling in atherosclerotic Apoe-/- mice were investigated by treatment with an agonistic IL-2Rβγ-targeting IL-2/anti-IL-2 complex or a monoclonal anti-CD122 (IL-2Rβ) blocking antibody.RESULTS: Administration of IL-2Rβγ agonistic IL-2/anti-IL-2 complexes to Apoe-/- mice augmented opposing arms of the adaptive immune system. Expansion of effector/memory T cells and increased levels of circulating pro-inflammatory cytokines were observed along with elevated levels of regulatory T cells and IL-10. Notably, IL-2/anti-IL-2 treatment did not affect plaque size but decreased levels of plasma cholesterol. The cholesterol lowering effect of IL-2Rβγ agonism was not affected by anti-CD8 or anti-NK1.1 depleting antibody treatment but was contingent on the presence of adaptive immunity. Expression of multiple liver X receptor (LXR)-related genes, including Pltp and Srebp1c in the liver, was decreased by IL-2/anti-IL-2 treatment. Although IL-2Rβγ agonism lowered cholesterol levels, blocking IL-2Rβγ signalling using an anti-CD122 monoclonal antibody did not impact cholesterol levels or plaque burden in Apoe-/- mice.CONCLUSIONS: Elevated IL-2Rβγ signalling results in activation of both inflammatory and regulatory lymphocytes with a net zero effect on atherosclerosis and decreased plasma cholesterol levels. Changes in cholesterol levels were associated with reductions in hepatic LXR-related gene expression. Further studies are needed to investigate the clinical significance of IL-2 mediated modulation of hepatic LXR signalling in inflammatory disorders.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- ref (ämneskategori)
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