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

Autor: Kamii Y; Department of Bacteriology, The Jikei University School of Medicine, Tokyo 105-8461, Japan.; Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan., Hayashizaki K; Department of Bacteriology, The Jikei University School of Medicine, Tokyo 105-8461, Japan.; Jikei Center for Biofilm Science and Technology, The Jikei University School of Medicine, Tokyo 105-8461, Japan., Kanno T; Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Chiba 292-0818, Japan., Chiba A; Department of Bacteriology, The Jikei University School of Medicine, Tokyo 105-8461, Japan.; Jikei Center for Biofilm Science and Technology, The Jikei University School of Medicine, Tokyo 105-8461, Japan., Ikegami T; Department of Bacteriology, The Jikei University School of Medicine, Tokyo 105-8461, Japan.; Department of Orthopaedic Surgery, The Jikei University School of Medicine, Tokyo 105-8461, Japan., Saito M; Department of Orthopaedic Surgery, The Jikei University School of Medicine, Tokyo 105-8461, Japan., Akeda Y; Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan., Ohteki T; Department of Biodefense Research, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan., Kubo M; Division of Molecular Pathology, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan., Yoshida K; Department of Biochemistry, The Jikei University School of Medicine, Tokyo 105-8461, Japan., Kawakami K; Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan., Oishi K; Toyama Institute of Health, Toyama 939-0363, Japan., Araya J; Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan., Kuwano K; Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan., Kronenberg M; La Jolla Institute for Immunology, La Jolla, CA 92037.; Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093., Endo Y; Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Chiba 292-0818, Japan., Kinjo Y; Department of Bacteriology, The Jikei University School of Medicine, Tokyo 105-8461, Japan.; Jikei Center for Biofilm Science and Technology, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
Jazyk: angličtina
Zdroj: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Feb 27; Vol. 121 (9), pp. e2313964121. Date of Electronic Publication: 2024 Feb 23.
DOI: 10.1073/pnas.2313964121
Abstrakt: Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that express an invariant T cell receptor α 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 (NKT FH ) cells are specialized to help B cells. However, the mechanisms of NKT FH cell differentiation remain to be elucidated. In this report, we studied the mechanism of NKT FH cell differentiation induced by pneumococcal surface protein A and α-galactosylceramide (P/A) vaccination. We found that Gr-1 + cells helped iNKT cell proliferation and NKT FH cell differentiation in the spleen by producing interleukin-27 (IL-27) in the early phase after vaccination. The neutralization of IL-27 impaired NKT FH 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 NKT FH cells. Interestingly, Gr-1 + cell-derived IL-27 was induced by iNKT cells via interferon-γ 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.
Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze: MEDLINE
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