Oleic acid enhances proliferation and calcium mobilization of CD3/CD28 activated CD4+ T cells through incorporation into membrane lipids

被引:0
|
作者
von Hegedus, Johannes Hendrick [1 ,2 ]
de Jong, Anja J. [1 ]
Hoekstra, Anna T. [3 ,4 ]
Spronsen, Eric [1 ]
Zhu, Wahwah [1 ]
Cabukusta, Birol [5 ]
Kwekkeboom, Joanneke C. [1 ]
Heijink, Marieke [6 ]
Bos, Erik [7 ]
Berkers, Celia R. [3 ]
Giera, Martin A. [6 ]
Toes, Rene E. M. [1 ]
Ioan-Facsinay, Andreea [1 ]
机构
[1] Leiden Univ, Med Ctr, Dept Rheumatol, Albinusdreef 2, NL-2300 RC Leiden, Netherlands
[2] Univ Utrecht, Fac Vet Med, Dept Clin Sci, Utrecht, Netherlands
[3] Univ Utrecht, Bijvoet Ctr Biomol Res, Biomol Mass Spectrometry & Prote, Utrecht, Netherlands
[4] Leiden Univ, Med Ctr, Dept Med, Div Endocrinol, Leiden, Netherlands
[5] Leiden Univ, Med Ctr, Oncode Inst, Dept Cell & Chem Biol, Leiden, Netherlands
[6] Leiden Univ, Med Ctr, Ctr Prote & Metabol, Leiden, Netherlands
[7] Leiden Univ, Med Ctr, Dept Cell & Chem Biol, Leiden, Netherlands
关键词
CD4 T cells; Cellular proliferation; Fatty acids; Immune regulation; Metabolomics; Oleic acid; TCR; FATTY-ACIDS; LYMPHOCYTE-PROLIFERATION; BINDING PROTEINS; CLICK CHEMISTRY; EXPRESSION; LIPOLYSIS;
D O I
10.1002/eji.202350685
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Unsaturated fatty acids (UFA) are crucial for T-cell effector functions, as they can affect the growth, differentiation, survival, and function of T cells. Nonetheless, the mechanisms by which UFA affects T-cell behavior are ill-defined. Therefore, we analyzed the processing of oleic acid, a prominent UFA abundantly present in blood, adipocytes, and the fat pads surrounding lymph nodes, in CD4(+) T cells. We found that exogenous oleic acid increases proliferation and enhances the calcium flux response upon CD3/CD28 activation. By using a variety of techniques, we found that the incorporation of oleic acid into membrane lipids, rather than regulation of cellular metabolism or TCR expression, is essential for its effects on CD4(+) T cells. These results provide novel insights into the mechanism through which exogenous oleic acid enhances CD4(+) T-cell function.
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页数:17
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