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

• Published in: European journal of immunology 2024-09, Vol.54 (9), p.e2350685-n/a
• Main Authors: Hegedus, Johannes Hendrick, Jong, Anja J., Hoekstra, Anna T., Spronsen, Eric, Zhu, Wahwah, Cabukusta, Birol, Kwekkeboom, Joanneke C., Heijink, Marieke, Bos, Erik, Berkers, Celia R., Giera, Martin A., Toes, Rene E. M., Ioan‐Facsinay, Andreea
• Format: Article
• Language: English
• Subjects: Adipocytes; Animals; Calcium - metabolism; Calcium mobilization; Calcium Signaling - drug effects; CD28 antigen; CD28 Antigens - immunology; CD28 Antigens - metabolism; CD3 antigen; CD3 Complex - immunology; CD3 Complex - metabolism; CD4 antigen; CD4 T cells; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell activation; Cell differentiation; Cell proliferation; Cell Proliferation - drug effects; Cell survival; Cells, Cultured; Cellular proliferation; Effector cells; Fatty acids; Humans; Immune regulation; Lipid metabolism; Lymph nodes; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Lymphocytes T; Membrane Lipids - metabolism; Metabolomics; Mice; Mice, Inbred C57BL; Oleic acid; Oleic Acid - pharmacology; TCR
• ISSN: 0014-2980; 1521-4141; 1521-4141
• DOI: 10.1002/eji.202350685

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. Exogenous oleic acid, an unsaturated fatty acid, increases the proliferation of CD3/CD28 activated CD4⁺ T cells by integrating into membrane lipids. Oleic acid increases proliferation via intracellular calcium signaling responses, rather than increased TCR signaling or metabolic pathway regulation.