423
Views
9
CrossRef citations to date
0
Altmetric
Short Communication

Inhibition of fatty acid metabolism by etomoxir or TOFA suppresses murine dendritic cell activation without affecting viability

ORCID Icon, & ORCID Icon
Pages 361-369 | Received 01 Mar 2019, Accepted 01 May 2019, Published online: 02 Jun 2019

References

  • Merad M, Sathe P, Helft J, et al. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol. 2013;31:563–604.
  • Guilliams M, Ginhoux F, Jakubzick C, et al. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat Rev Immunol. 2014;14:571–578.
  • Gallo PM, Gallucci S. The dendritic cell response to classic, emerging, and homeostatic danger signals. Implications for autoimmunity. Front Immunol. 2013;4:138.
  • Ganguly D, Haak S, Sisirak V, et al. The role of dendritic cells in autoimmunity. Nat Rev Immunol. 2013;13:566–577.
  • Quintana FJ. Dendritic cells in autoimmunity, infections, and cancer. Semin Immunopathol. 2017;39:97–98.
  • Mbongue J, Nicholas D, Firek A, et al. The role of dendritic cells in tissue-specific autoimmunity. J Immunol Res. 2014;2014:1.
  • Drakesmith H, Chain B, Beverley P. How can dendritic cells cause autoimmune disease? Immunol Today. 2000;21:214–217.
  • Amodio G, Gregori S. Dendritic cells a double-edge sword in autoimmune responses. Front Immunol. 2012;3:233.
  • Hardin JA. Dendritic cells: potential triggers of autoimmunity and targets for therapy. Ann Rheum Dis. 2005;64:iv86–iv90.
  • Crow MK. Type I interferon in the pathogenesis of lupus. J Immunol. 2014;192:5459–5468.
  • Rönnblom L, Alm GV, Eloranta ML. Type I interferon and lupus. Curr Opin Rheumatol. 2009;21:471–477.
  • Bennett L, Palucka AK, Arce E, et al. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med. 2003;197:711–723.
  • Obermoser G, Pascual V. The interferon-alpha signature of systemic lupus erythematosus. Lupus. 2010;19:1012–1019.
  • Guiducci C, Gong M, Xu Z, et al. TLR recognition of self-nucleic acids hampers glucocorticoid activity in lupus. Nature. 2010;465:937–941.
  • Colonna L, Dinnall JA, Shivers DK, et al. Abnormal costimulatory phenotype and function of dendritic cells before and after the onset of severe murine lupus. Arthritis Res Ther. 2006;8:R49.
  • Sriram U, Varghese L, Bennett HL, et al. Myeloid dendritic cells from B6.NZM Sle1/Sle2/Sle3 lupus-prone mice express an IFN signature that precedes disease onset. J Immunol. 2012;189:80–91.
  • Lupus Foundation of America, Inc [Internet]. Fact sheet. 2001. Available from: https://www.lupus.org/resources/what-is-lupus.
  • Kaul A, Gordon C, Crow MK, et al. Systemic lupus erythematosus. Nat Rev Dis Primers. 2016;2:16039.
  • Dolgin E. Lupus in crisis: as failures pile up, clinicians call for new tools. Nat Biotechnol. 2019;37:7–8.
  • Perl A. Review: metabolic control of immune system activation in rheumatic diseases. Arthritis Rheumatol. 2017;69:2259–2270.
  • Geltink RIK, Kyle RL, Pearce EL. Unraveling the complex interplay between T cell metabolism and function. Annu Rev Immunol. 2018;36:461–488.
  • O'Neill LA, Pearce EJ. Immunometabolism governs dendritic cell and macrophage function. J Exp Med. 2016;213:15–23.
  • Yin Y, Choi SC, Xu Z, et al. Normalization of CD4+ T cell metabolism reverses lupus. Sci Transl Med. 2015;7:274ra18.
  • Wu D, Sanin DE, Everts B, et al. Type 1 interferons induce changes in core metabolism that are critical for immune function. Immunity. 2016;44:1325–1336.
  • Everts B, Amiel E, van der Windt GJ, et al. Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells. Blood. 2012;120:1422–1431.
  • Chakhtoura M, Chain RW, Sato PY, et al. Ethyl pyruvate modulates murine dendritic cell activation and survival through their immunometabolism. Front Immunol. 2019;10:30.
  • Pike LS, Smift AL, Croteau NJ, et al. Inhibition of fatty acid oxidation by etomoxir impairs NADPH production and increases reactive oxygen species resulting in ATP depletion and cell death in human glioblastoma cells. Biochim Biophys Acta 2011;1807:726–734.
  • Guseva NV, Rokhlin OW, Glover RA, et al. TOFA (5-tetradecyl-oxy-2-furoic acid) reduces fatty acid synthesis, inhibits expression of AR, neuropilin-1 and Mcl-1 and kills prostate cancer cells independent of p53 status. Cancer Biol Ther. 2011;12:80–85.
  • Herber DL, Cao W, Nefedova Y, et al. Lipid accumulation and dendritic cell dysfunction in cancer. Nat Med. 2010;16:880–886.
  • Gallo PM, Rapsinski GJ, Wilson RP, et al. Amyloid-DNA composites of bacterial biofilms stimulate autoimmunity. Immunity. 2015;42:1171–1184.
  • Xu J, Lee MH, Chakhtoura M, et al. STAT2 is required for TLR-induced murine dendritic cell activation and cross-presentation. J Immunol. 2016;197:326–336.
  • Sriram U, Biswas C, Behrens EM, et al. IL-4 suppresses dendritic cell response to type I interferons. J Immunol. 2007;179:6446–6455.
  • Sriram U, Xu J, Chain RW, et al. IL-4 suppresses the responses to TLR7 and TLR9 stimulation and increases the permissiveness to retroviral infection of murine conventional dendritic cells. PLoS One. 2014;9:e87668.
  • Shriver LP, Manchester M. Inhibition of fatty acid metabolism ameliorates disease activity in an animal model of multiple sclerosis. Sci Rep. 2011;1:79.
  • Hossain F, Al-Khami AA, Wyczechowska D, et al. Inhibition of fatty acid oxidation modulates immunosuppressive functions of myeloid-derived suppressor cells and enhances cancer therapies. Cancer Immunol Res. 2015;3:1236–1247.
  • Zhu J, Liu X, Xie C, et al. T cell hyperactivity in lupus as a consequence of hyperstimulatory antigen-presenting cells. J Clin Invest. 2005;115:1869–1878.
  • Ding D, Mehta H, McCune WJ, et al. Aberrant phenotype and function of myeloid dendritic cells in systemic lupus erythematosus. J Immunol. 2006;177:5878–5889.
  • Fransen JH, Vlag J, Ruben J, et al. The role of dendritic cells in the pathogenesis of systemic lupus erythematosus. Arthritis Res Ther. 2010;12:207.
  • Abdel Galil SM, Ezzeldin N, El-Boshy ME. The role of serum IL-17 and IL-6 as biomarkers of disease activity and predictors of remission in patients with lupus nephritis. Cytokine. 2015;76:280–287.
  • Lee MH, Chakhtoura M, Sriram U, et al. Conventional DCs from male and female lupus-prone B6.NZM Sle1/Sle2/Sle3 mice express an IFN signature and have a higher immunometabolism that are enhanced by estrogen. J Immunol Res. 2018;2018:1.
  • Pearce EL, Pearce EJ. Metabolic pathways in immune cell activation and quiescence. Immunity. 2013;38:633–643.
  • Steinman RM. Linking innate to adaptive immunity through dendritic cells. Novartis Found Symp. 2006;279:101–109. discussion 109–113, 216–219.
  • Ganeshan K, Chawla A. Metabolic regulation of immune responses. Annu Rev Immunol. 2014;32:609–634.
  • Decker P, Kötter I, Klein R, et al. Monocyte-derived dendritic cells over-express CD86 in patients with systemic lupus erythematosus. Rheumatology. 2006;45:1087–1095.
  • Brahmakshatriya V, Kuang Y, Devarajan P, et al. IL-6 production by TLR-activated APC broadly enhances aged cognate CD4 helper and B cell antibody responses in vivo. J Immunol. 2017;198:2819–2833.
  • Ohl K, Tenbrock K. Inflammatory cytokines in systemic lupus erythematosus. J Biomed Biotechnol. 2011;2011:1.
  • Bauer JW, Baechler EC, Petri M, et al. Elevated serum levels of interferon-regulated chemokines are biomarkers for active human systemic lupus erythematosus. PLoS Med. 2006;3:e491.
  • Andrade F, Akhter E, Fang H, et al. ABSTRACT NUMBER: 619 elevated plasma levels of CXCL2 and CXCL10 have distinct predictive value in systemic lupus erythematosus. Am Coll Rheumatol. 2012;64:619.
  • Timmers S, Nabben M, Bosma M, et al. Augmenting muscle diacylglycerol and triacylglycerol content by blocking fatty acid oxidation does not impede insulin sensitivity. Proc Natl Acad Sci USA. 2012;109:11711–11716.
  • Briant LJB, Dodd MS, Chibalina MV, et al. CPT1a-dependent long-chain fatty acid oxidation contributes to maintaining glucagon secretion from pancreatic islets. Cell Rep. 2018;23:3300–3311.
  • Ibitokou SA, Dillon BE, Sinha M, et al. Early inhibition of fatty acid synthesis reduces generation of memory precursor effector T cells in chronic infection. J Immunol. 2018;200:643–656.
  • Van den Bossche J, van der Windt GJW. Fatty acid oxidation in macrophages and T cells: time for reassessment? Cell Metab. 2018;28:538–540.
  • van der Windt GJ, Everts B, Chang CH, et al. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity. 2012;36:68–78.
  • Divakaruni AS, Hsieh WY, Minarrieta L, et al. Etomoxir inhibits macrophage polarization by disrupting CoA homeostasis. Cell Metab. 2018;28:490.e7–503.e7.
  • Samudio I, Harmancey R, Fiegl M, et al. Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. J Clin Invest. 2010;120:142–156.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.