IL-27 regulates the differentiation of follicular helper NKT cells via metabolic adaptation of mitochondria

• 成果类型: Article
• 署名作者: Kamii, Yasuhiro; Hayashizaki, Koji; Kanno, Toshio; Chiba, Akio; Ikegami, Taku; Saito, Mitsuru; Akeda, Yukihiro; Ohteki, Toshiaki; Kubo, Masato; Yoshida, Kiyotsugu; Kawakami, Kazuyoshi; Oishi, Kazunori; Araya, Jun; Kuwano, Kazuyoshi; Kronenberg, Mitchell; Endo, Yusuke; Kinjo, Yuki
• 署名单位: Jikei University; Jikei University; Jikei University; Kazusa DNA Research Institute; Jikei University; Japan Institute for Health Security (JIHS); National Institute of Infectious Diseases (NIID); Institute of Science Tokyo; Tokyo Medical & Dental University (TMDU); Tokyo University of Science; Jikei University; Tohoku University; La Jolla Institute for Immunology; University of California System; University of California San Diego
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13729
• DOI: 10.1073/pnas.2313964121
• 发表日期: 2024-02-27
• 关键词: protein-a pspa; killer t-cells; surface protein; innate; expression; immunity; biology

摘要

Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that express an invariant T cell receptor alpha chain and contribute to bridging innate and acquired immunity with rapid production of large amounts of cytokines after stimulation. Among effecter subsets of iNKT cells, follicular helper NKT (NKTFH) cells are specialized to help B cells. However, the mechanisms of NKTFH cell differentiation remain to be elucidated. In this report, we studied the mechanism of NKTFH cell differentiation induced by pneumococcal surface protein A and alpha- galactosylceramide (P/A) vaccination. We found that Gr-1+ cells helped iNKT cell proliferation and NKTFH cell differentiation in the spleen by producing interleukin-27 (IL-27) in the early phase after vaccination. The neutralization of IL-27 impaired NKTFH cell differentiation, which resulted in compromised antibody production and diminished protection against Streptococcus pneumoniae infection by the P/A vaccine. Our data indicated that Gr-1+ cell-derived IL-27 stimulated mitochondrial metabolism, meeting the energic demand required for iNKT cells to differentiate into NKTFH cells. Interestingly, Gr-1+ cell-derived IL-27 was induced by iNKT cells via interferon-gamma production. Collectively, our findings suggest that optimizing the metabolism of iNKT cells was essential for acquiring specific effector functions, and they provide beneficial knowledge on iNKT cell-mediated vaccination- mediated therapeutic strategies.