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, 42 (11), 747-754

Cellular and Molecular Links Between Autoimmunity and Lipid Metabolism

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Cellular and Molecular Links Between Autoimmunity and Lipid Metabolism

Heeju Ryu et al. Mol Cells.

Abstract

The incidence of atherosclerosis is higher among patients with several autoimmune diseases such as psoriasis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It is well documented that innate immune cells including macrophages and dendritic cells sense lipid species such as saturated fatty acids and oxidized low-density lipoprotein and produce pro-inflammatory cytokines and chemokines. However, whether a hyperlipidemic environment also impacts autoimmune T cell responses has been unclear. Among CD4+ T cells, Th17 and follicular helper T (Tfh) cells are known to play pathogenic roles in the development of hyperlipidemiaassociated autoimmune diseases. This review gives an overview of the cellular and molecular mechanisms by which dysregulated lipid metabolism impacts the pathogenesis of autoimmune diseases, with specific emphasis on Th17 and Tfh cells.

Keywords: Tfh cell; Th17 cell; autoimmune diseases; hyperlipidemia; lipid metabolism.

Conflict of interest statement

Disclosure

The authors have no potential conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1. Differentiation of Th17 and Tfh cells
Upon the stimulation by dendritic cells, naive CD4+ T cells can be activated and differentiated into Th17 and Tfh cells based on the cytokine environment they are exposed to. Aberrant activation of Th17 and Tfh cells can raise autoimmunity.
Fig. 2
Fig. 2. Links between atherosclerosis and autoimmune diseases
Patients with systemic autoimmune disorders show an increased incidence of atherosclerosis; these hyperlipidemia-associated autoimmune diseases include psoriasis, rheumatoid arthritis, and systemic lupus erythematosus. Cholesterol-lowering treatment has been shown to ameliorate psoriasis and systemic lupus erythematosus, suggesting a detrimental role of hyperlipidemia in the autoimmune disease.
Fig. 3
Fig. 3. Modulation of autoreactive Th17 and Tfh cells by hyperlipidemia
Hyperlipidemia induces accumulation of lipid species in DCs, which augments the production of proinflammatory cytokines. These cytokines enhance the differentiation of autoreactive Th17 and Tfh cells.
Fig. 4
Fig. 4. Possible mechanisms underlying how hyperlipidemia modulates dendritic cell functions
Atherogenic dyslipidemia augments the production of pro-inflammatory cytokines through the increase of circulating lipid species, regulation of innate receptors, and inhibition of NF-κB signaling.

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References

    1. A-Gonzalez N., Bensinger S.J., Hong C., Beceiro S., Bradley M.N., Zelcer N., Deniz J., Ramirez C., Díaz M., Gallardo G., et al. Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR. Immunity. 2009;31:245–258. doi: 10.1016/j.immuni.2009.06.018. - DOI - PMC - PubMed
    1. Ait-Oufella H., Salomon B.L., Potteaux S., Robertson A.K.L., Gourdy P., Zoll J., Merval R., Esposito B., Cohen J.L., Fisson S., et al. Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med. 2006;12:178–180. doi: 10.1038/nm1343. - DOI - PubMed
    1. Aktas O., Waiczies S., Smorodchenko A., Dorr J., Seeger B., Prozorovski T., Sallach S., Endres M., Brocke S., Nitsch R., et al. Treatment of relapsing paralysis in experimental encephalomyelitis by targeting Th1 cells through atorvastatin. J Exp Med. 2003;197:725–733. doi: 10.1084/jem.20021425. - DOI - PMC - PubMed
    1. Anaya J.M. Common mechanisms of autoimmune diseases (the autoimmune tautology) Autoimmun Rev. 2012;11:781–784. doi: 10.1016/j.autrev.2012.02.002. - DOI - PubMed
    1. Bao Y.K., Weide L.G., Ganesan V.C., Jakhar I., McGill J.B., Sahil S., Cheng A.L., Gaddis M., Drees B.M. High prevalence of comorbid autoimmune diseases in adults with type 1 diabetes from the HealthFacts database. J Diabetes. 2019;11:273–279. doi: 10.1111/1753-0407.12856. - DOI - PubMed
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