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.) |
References: | Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, et al. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia. 2007;55:453–62. (PMID: 17203472287168510.1002/glia.20467) Zhao J, Bi W, Xiao S, Lan X, Cheng X, Zhang J, et al. Neuroinflammation induced by lipopolysaccharide causes cognitive impairment in mice. Sci Rep. 2019;9:5790. (PMID: 30962497645393310.1038/s41598-019-42286-8) Thomson CA, McColl A, Graham GJ, Cavanagh J. Sustained exposure to systemic endotoxin triggers chemokine induction in the brain followed by a rapid influx of leukocytes. J Neuroinflammation. 2020;17:94. (PMID: 32213184709813510.1186/s12974-020-01759-8) He H, Geng T, Chen P, Wang M, Hu J, Kang L, et al. NK cells promote neutrophil recruitment in the brain during sepsis-induced neuroinflammation. Sci Rep. 2016;6:27711. (PMID: 27270556489769210.1038/srep27711) Lee SW, Park HJ, Van Kaer L, Hong S. Roles and therapeutic potential of CD1d-Restricted NKT cells in inflammatory skin diseases. Front Immunol. 2022;13: 979370. (PMID: 36119077947817410.3389/fimmu.2022.979370) Van Kaer L, Wu L. Therapeutic Potential of Invariant Natural Killer T Cells in Autoimmunity. Front Immunol. 2018;9:519. (PMID: 29593743585901710.3389/fimmu.2018.00519) Lee YJ, Holzapfel KL, Zhu J, Jameson SC, Hogquist KA. Steady-state production of IL-4 modulates immunity in mouse strains and is determined by lineage diversity of iNKT cells. Nat Immunol. 2013;14:1146–54. (PMID: 2409711010.1038/ni.2731) Uchida T, Nakashima H, Yamagata A, Ito S, Ishikiriyama T, Nakashima M, et al. Repeated administration of alpha-galactosylceramide ameliorates experimental lupus nephritis in mice. Sci Rep. 2018;8:8225. (PMID: 29844470597423010.1038/s41598-018-26470-w) Horikoshi M, Goto D, Segawa S, Yoshiga Y, Iwanami K, Inoue A, et al. Activation of Invariant NKT cells with glycolipid ligand alpha-galactosylceramide ameliorates glucose-6-phosphate isomerase peptide-induced arthritis. PLoS ONE. 2012;7: e51215. (PMID: 23251456352096410.1371/journal.pone.0051215) Coppieters K, Van Beneden K, Jacques P, Dewint P, Vervloet A, Vander Cruyssen B, et al. A single early activation of invariant NK T cells confers long-term protection against collagen-induced arthritis in a ligand-specific manner. J Immunol. 2007;179:2300–9. (PMID: 1767549110.4049/jimmunol.179.4.2300) Sag D, Krause P, Hedrick CC, Kronenberg M, Wingender G. IL-10-producing NKT10 cells are a distinct regulatory invariant NKT cell subset. J Clin Invest. 2014;124:3725–40. (PMID: 25061873415120310.1172/JCI72308) Park HJ, Kim TC, Park YH, Lee SW, Jeon J, Park SH, et al. Repeated alpha-GalCer administration induces a type 2 cytokine-biased iNKT Cell response and exacerbates atopic skin inflammation in valpha14(Tg) NC/Nga Mice. Biomedicines. 2021;9:1619. (PMID: 34829848861598410.3390/biomedicines9111619) Wingender G, Sag D, Kronenberg M. NKT10 cells: a novel iNKT cell subset. Oncotarget. 2015;6:26552–3. (PMID: 26337343469493210.18632/oncotarget.5270) Lynch L, Michelet X, Zhang S, Brennan PJ, Moseman A, Lester C, et al. Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of T(reg) cells and macrophages in adipose tissue. Nat Immunol. 2015;16:85–95. (PMID: 2543697210.1038/ni.3047) Chen D, Zhao H, Gao X, Chen S, Liu H, Zhang J, et al. Subcutaneous administration of alpha-GalCer activates iNKT10 cells to promote M2 macrophage polarization and ameliorates chronic inflammation of obese adipose tissue. Int Immunopharmacol. 2019;77: 105948. (PMID: 3162921610.1016/j.intimp.2019.105948) Yshii L, Pasciuto E, Bielefeld P, Mascali L, Lemaitre P, Marino M, et al. Astrocyte-targeted gene delivery of interleukin 2 specifically increases brain-resident regulatory T cell numbers and protects against pathological neuroinflammation. Nat Immunol. 2022;23:878–91. (PMID: 35618831917405510.1038/s41590-022-01208-z) Ito M, Komai K, Mise-Omata S, Iizuka-Koga M, Noguchi Y, Kondo T, et al. Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery. Nature. 2019;565:246–50. (PMID: 3060278610.1038/s41586-018-0824-5) Spath S, Roan F, Presnell SR, Hollbacher B, Ziegler SF. Profiling of Tregs across tissues reveals plasticity in ST2 expression and hierarchies in tissue-specific phenotypes. iScience. 2022;25:104998. (PMID: 36093048946083310.1016/j.isci.2022.104998) Xie D, Miao W, Xu F, Yuan C, Li S, Wang C, et al. IL-33/ST2 axis protects against traumatic brain injury through enhancing the function of regulatory T cells. Front Immunol. 2022;13: 860772. (PMID: 35432343900695010.3389/fimmu.2022.860772) Hua J, Liang S, Ma X, Webb TJ, Potter JP, Li Z. The interaction between regulatory T cells and NKT cells in the liver: a CD1d bridge links innate and adaptive immunity. PLoS ONE. 2011;6: e27038. (PMID: 22073248320688210.1371/journal.pone.0027038) Lee SW, Park HJ, Cheon JH, Wu L, Van Kaer L, Hong S. iNKT cells suppress pathogenic NK1.1(+)CD8(+) T cells in DSS-induced colitis. Front Immunol. 2018;9:2168. (PMID: 30333822617607210.3389/fimmu.2018.02168) Halpert G, Eitan T, Voronov E, Apte RN, Rath-Wolfson L, Albeck M, et al. Multifunctional activity of a small tellurium redox immunomodulator compound, AS101, on dextran sodium sulfate-induced murine colitis. J Biol Chem. 2014;289:17215–27. (PMID: 24764299405916210.1074/jbc.M113.536664) Kalechman Y, Gafter U, Gal R, Rushkin G, Yan D, Albeck M, et al. Anti-IL-10 therapeutic strategy using the immunomodulator AS101 in protecting mice from sepsis-induced death: dependence on timing of immunomodulating intervention. J Immunol. 2002;169:384–92. (PMID: 1207726810.4049/jimmunol.169.1.384) Li X, Han Z, Wang F, Qiao J. The STAT6 inhibitor AS1517499 reduces the risk of asthma in mice with 2,4-dinitrochlorobenzene-induced atopic dermatitis by blocking the STAT6 signaling pathway. Allergy Asthma Clin Immunol. 2022;18:12. (PMID: 35177102885182710.1186/s13223-022-00652-8) Lee YJ, Kim K, Kim M, Ahn YH, Kang JL. Inhibition of STAT6 activation by AS1517499 inhibits expression and activity of PPARgamma in macrophages to resolve acute inflammation in mice. Biomolecules. 2022;12:447. (PMID: 35327639894651510.3390/biom12030447) Lee SW, Oh SY, Park HJ, Kim TC, Park YH, Van Kaer L, et al. Phosphorothioate-linked guanine/cytosine-based stem-loop oligonucleotides induce the extracellular release of mitochondrial DNA from peritoneal B1a cells. Int J Biol Macromol. 2022;223:252–62. (PMID: 3634736510.1016/j.ijbiomac.2022.10.280) Park HJ, Lee SW, Van Kaer L, Lee MS, Hong S. IL-7 deficiency exacerbates atopic dermatitis in NC/Nga mice. Int J Mol Sci. 2023;24:9956. (PMID: 373731041029819310.3390/ijms24129956) Lee SW, Park HJ, Van Kaer L, Hong S. Opposing roles of DCs and iNKT cells in the induction of Foxp3 expression by MLN CD25(+)CD4(+) T cells during IFNgamma-driven colitis. Int J Mol Sci. 2022;23:15316. (PMID: 36499642973888810.3390/ijms232315316) Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008;9:46–56. (PMID: 18073775291927710.1038/nrn2297) Kim EY, Ner-Gaon H, Varon J, Cullen AM, Guo J, Choi J, et al. Post-sepsis immunosuppression depends on NKT cell regulation of mTOR/IFN-gamma in NK cells. J Clin Invest. 2020;130:3238–52. (PMID: 32154791726000610.1172/JCI128075) Crosby CM, Kronenberg M. Tissue-specific functions of invariant natural killer T cells. Nat Rev Immunol. 2018;18:559–74. (PMID: 29967365634347510.1038/s41577-018-0034-2) Seki T, Kumagai T, Kwansa-Bentum B, Furushima-Shimogawara R, Anyan WK, Miyazawa Y, et al. Interleukin-4 (IL-4) and IL-13 suppress excessive neutrophil infiltration and hepatocyte damage during acute murine schistosomiasis japonica. Infect Immun. 2012;80:159–68. (PMID: 22038918325566410.1128/IAI.05581-11) Sun L, Guo RF, Newstead MW, Standiford TJ, Macariola DR, Shanley TP. Effect of IL-10 on neutrophil recruitment and survival after Pseudomonas aeruginosa challenge. Am J Respir Cell Mol Biol. 2009;41:76–84. (PMID: 1909798210.1165/rcmb.2008-0202OC) Sonderegger FL, Ma Y, Maylor-Hagan H, Brewster J, Huang X, Spangrude GJ, et al. Localized production of IL-10 suppresses early inflammatory cell infiltration and subsequent development of IFN-gamma-mediated Lyme arthritis. J Immunol. 2012;188:1381–93. (PMID: 2218061710.4049/jimmunol.1102359) Kramer TJ, Hack N, Bruhl TJ, Menzel L, Hummel R, Griemert EV, et al. Depletion of regulatory T cells increases T cell brain infiltration, reactive astrogliosis, and interferon-gamma gene expression in acute experimental traumatic brain injury. J Neuroinflammation. 2019;16:163. (PMID: 31383034668351610.1186/s12974-019-1550-0) Kwon HS, Koh SH. Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes. Transl Neurodegener. 2020;9:42. (PMID: 33239064768998310.1186/s40035-020-00221-2) Zhang W, Xiao D, Mao Q, Xia H. Role of neuroinflammation in neurodegeneration development. Signal Transduct Target Ther. 2023;8:267. (PMID: 374337681033614910.1038/s41392-023-01486-5) Zhan X, Stamova B, Sharp FR. Lipopolysaccharide associates with amyloid plaques, neurons and oligodendrocytes in Alzheimer’s disease brain: a review. Front Aging Neurosci. 2018;10:42. (PMID: 29520228582715810.3389/fnagi.2018.00042) He XF, Li LL, Xian WB, Li MY, Zhang LY, Xu JH, et al. Chronic colitis exacerbates NLRP3-dependent neuroinflammation and cognitive impairment in middle-aged brain. J Neuroinflammation. 2021;18:153. (PMID: 34229722826201710.1186/s12974-021-02199-8) Shimada A, Hasegawa-Ishii S. Increased cytokine expression in the choroid plexus stroma and epithelium in response to endotoxin-induced systemic inflammation in mice. Toxicol Rep. 2021;8:520–8. (PMID: 33747797797313710.1016/j.toxrep.2021.03.002) Lee SW, Park HJ, Van Kaer L, Hong S, Hong S. Graphene oxide polarizes iNKT cells for production of TGFbeta and attenuates inflammation in an iNKT cell-mediated sepsis model. Sci Rep. 2018;8:10081. (PMID: 29973666603160810.1038/s41598-018-28396-9) Biburger M, Tiegs G. Activation-induced NKT cell hyporesponsiveness protects from alpha-galactosylceramide hepatitis and is independent of active transregulatory factors. J Leukoc Biol. 2008;84:264–79. (PMID: 1840796710.1189/jlb.0607352) Brennan PJ, Tatituri RV, Brigl M, Kim EY, Tuli A, Sanderson JP, et al. Invariant natural killer T cells recognize lipid self antigen induced by microbial danger signals. Nat Immunol. 2011;12:1202–11. (PMID: 22037601324244910.1038/ni.2143) Darmoise A, Teneberg S, Bouzonville L, Brady RO, Beck M, Kaufmann SH, et al. Lysosomal alpha-galactosidase controls the generation of self lipid antigens for natural killer T cells. Immunity. 2010;33:216–28. (PMID: 20727792401830410.1016/j.immuni.2010.08.003) Lombardi V, Stock P, Singh AK, Kerzerho J, Yang W, Sullivan BA, et al. A CD1d-dependent antagonist inhibits the activation of invariant NKT cells and prevents development of allergen-induced airway hyperreactivity. J Immunol. 2010;184:2107–15. (PMID: 2008365610.4049/jimmunol.0901208) Chen Z, Lund R, Aittokallio T, Kosonen M, Nevalainen O, Lahesmaa R. Identification of novel IL-4/Stat6-regulated genes in T lymphocytes. J Immunol. 2003;171:3627–35. (PMID: 1450066010.4049/jimmunol.171.7.3627) Kashiwada M, Levy DM, McKeag L, Murray K, Schroder AJ, Canfield SM, et al. IL-4-induced transcription factor NFIL3/E4BP4 controls IgE class switching. Proc Natl Acad Sci U S A. 2010;107:821–6. (PMID: 2008075910.1073/pnas.0909235107) Weston LL, Jiang S, Chisholm D, Jantzie LL, Bhaskar K. Interleukin-10 deficiency exacerbates inflammation-induced tau pathology. J Neuroinflammation. 2021;18:161. (PMID: 34275478828662110.1186/s12974-021-02211-1) Gravel M, Beland LC, Soucy G, Abdelhamid E, Rahimian R, Gravel C, et al. IL-10 controls early microglial phenotypes and disease onset in ALS caused by misfolded superoxide dismutase 1. J Neurosci. 2016;36:1031–48. (PMID: 26791230660199910.1523/JNEUROSCI.0854-15.2016) O’Neil SM, Hans EE, Jiang S, Wangler LM, Godbout JP. Astrocyte immunosenescence and deficits in interleukin 10 signaling in the aged brain disrupt the regulation of microglia following innate immune activation. Glia. 2022;70:913–34. (PMID: 3506129710.1002/glia.24147) Shemer A, Scheyltjens I, Frumer GR, Kim JS, Grozovski J, Ayanaw S, et al. Interleukin-10 prevents pathological microglia hyperactivation following peripheral endotoxin challenge. Immunity. 2020;53(1033–1049): e7. Dardalhon V, Awasthi A, Kwon H, Galileos G, Gao W, Sobel RA, et al. IL-4 inhibits TGF-beta-induced Foxp3+ T cells and together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells. Nat Immunol. 2008;9:1347–55. (PMID: 18997793299900610.1038/ni.1677) |
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 |
تدمد: | 1420-908X |
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DOI: | 10.1007/s00011-024-01915-3 |