دورية أكاديمية
Alpha-galactosylceramide pre-treatment attenuates clinical symptoms of LPS-induced acute neuroinflammation by converting pathogenic iNKT cells to anti-inflammatory iNKT10 cells in the brain.
| العنوان: | Alpha-galactosylceramide pre-treatment attenuates clinical symptoms of LPS-induced acute neuroinflammation by converting pathogenic iNKT cells to anti-inflammatory iNKT10 cells in the brain. |
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| المؤلفون: | Kim TC; Department of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, 209 Neungdong-ro, Gwangjin-gu, Seoul, 05006, South Korea., Park HJ; Department of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, 209 Neungdong-ro, Gwangjin-gu, Seoul, 05006, South Korea., Lee SW; Department of Biomedical Laboratory Science, College of Health and Biomedical Services, Sangji University, Wonju, 26339, South Korea., Park YH; Department of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, 209 Neungdong-ro, Gwangjin-gu, Seoul, 05006, South Korea., Van Kaer L; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA., Hong S; Department of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, 209 Neungdong-ro, Gwangjin-gu, Seoul, 05006, South Korea. shong@sejong.ac.kr. |
| المصدر: | Inflammation research : official journal of the European Histamine Research Society ... [et al.] [Inflamm Res] 2024 Sep; Vol. 73 (9), pp. 1511-1527. Date of Electronic Publication: 2024 Jul 19. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Birkhäuser Country of Publication: Switzerland NLM ID: 9508160 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1420-908X (Electronic) Linking ISSN: 10233830 NLM ISO Abbreviation: Inflamm Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Basel, Switzerland : Birkhäuser, c1995- |
| مواضيع طبية MeSH: | Galactosylceramides*/pharmacology , Lipopolysaccharides* , Natural Killer T-Cells*/immunology , Natural Killer T-Cells*/drug effects , Mice, Inbred C57BL* , Brain*/pathology , Brain*/drug effects , Brain*/immunology , Neuroinflammatory Diseases*/drug therapy , Neuroinflammatory Diseases*/immunology , Neuroinflammatory Diseases*/chemically induced, Animals ; Male ; Mice ; Cytokines/metabolism |
| مستخلص: | Background: Invariant natural killer T (iNKT) cells play protective or pathogenic roles in a variety of immune and inflammatory diseases. However, whether iNKT cells contribute to the progression of acute neuroinflammation remains unclear. Thus, we addressed this question with a mouse model of lipopolysaccharide (LPS)-induced acute neuroinflammation. Methods: For induction of acute neuroinflammation, wild-type (WT) C57BL/6 (B6) mice were injected intraperitoneally (i.p.) with LPS for either three or five consecutive days, and then these mice were analyzed for brain-infiltrating leukocytes or mouse behaviors, respectively. To examine the role of iNKT cell activation in LPS-induced neuroinflammation, mice were injected i.p. with the iNKT cell agonist α-galactosylceramide (α-GalCer) seven days prior to LPS treatment. Immune cells infiltrated into the brain during LPS-induced neuroinflammation were determined by flow cytometry. In addition, LPS-induced clinical behavior symptoms such as depressive-like behavior and memory impairment in mice were evaluated by the open field and Y-maze tests, respectively. Results: We found that iNKT cell-deficient Jα18 mutant mice display delayed disease progression and decreased leukocyte infiltration into the brain compared with WT mice, indicating that iNKT cells contribute to the pathogenesis of LPS-induced neuroinflammation. Since it has been reported that pre-treatment with α-GalCer, an iNKT cell agonist, can convert iNKT cells towards anti-inflammatory phenotypes, we next explored whether pre-activation of iNKT cells with α-GalCer can regulate LPS-induced neuroinflammation. Strikingly, we found that α-GalCer pre-treatment significantly delays the onset of clinical symptoms, including depression-like behavior and memory impairment, while decreasing brain infiltration of pro-inflammatory natural killer cells and neutrophils, in this model of LPS-induced neuroinflammation. Such anti-inflammatory effects of α-GalCer pre-treatment closely correlated with iNKT cell polarization towards IL4- and IL10-producing phenotypes. Furthermore, α-GalCer pre-treatment restored the expression of suppressive markers on brain regulatory T cells during LPS-induced neuroinflammation. Conclusion: Our findings provide strong evidence that α-GalCer-induced pre-activation of iNKT cells expands iNKT10 cells, mitigating depressive-like behaviors and brain infiltration of inflammatory immune cells induced by LPS-induced acute neuroinflammation. Thus, we suggest the prophylactic potential of iNKT cells and α-GalCer against acute neuroinflammation. (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.) |
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| معلومات مُعتمدة: | NRF-2021R1I1A1A01051465 National Research Foundation of Korea; NRF-2021R1I1A1A01054418 National Research Foundation of Korea; NRF-2019R1A2C1009926 National Research Foundation of Korea |
| فهرسة مساهمة: | Keywords: Alpha-galactosylceramide; IL10; Lipopolysaccharide; NK cells; Neuroinflammation; Neutrophils; Regulatory T cells; iNKT cells |
| المشرفين على المادة: | 0 (Galactosylceramides) 0 (alpha-galactosylceramide) 0 (Lipopolysaccharides) 0 (Cytokines) |
| تواريخ الأحداث: | Date Created: 20240719 Date Completed: 20240827 Latest Revision: 20240827 |
| رمز التحديث: | 20240828 |
| DOI: | 10.1007/s00011-024-01915-3 |
| PMID: | 39028491 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1420-908X |
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| DOI: | 10.1007/s00011-024-01915-3 |