دورية أكاديمية
Tofacitinib Treatment Suppresses CD4+ T-Cell Activation and Th1 Response, Contributing to Protection against Staphylococcal Toxic Shock.
العنوان: | Tofacitinib Treatment Suppresses CD4+ T-Cell Activation and Th1 Response, Contributing to Protection against Staphylococcal Toxic Shock. |
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المؤلفون: | Jarneborn A; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 46 Gothenburg, Sweden.; Department of Rheumatology, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden., Hu Z; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 46 Gothenburg, Sweden., Deshmukh M; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 46 Gothenburg, Sweden., Kopparapu PK; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 46 Gothenburg, Sweden., Jin T; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 46 Gothenburg, Sweden.; Department of Rheumatology, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden. |
المصدر: | International journal of molecular sciences [Int J Mol Sci] 2024 Jul 07; Vol. 25 (13). Date of Electronic Publication: 2024 Jul 07. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI, [2000- |
مواضيع طبية MeSH: | Piperidines*/pharmacology , Piperidines*/therapeutic use , Th1 Cells*/immunology , Th1 Cells*/drug effects , Th1 Cells*/metabolism , Pyrimidines*/pharmacology , Pyrimidines*/therapeutic use , Shock, Septic*/drug therapy , Shock, Septic*/immunology , Shock, Septic*/chemically induced , CD4-Positive T-Lymphocytes*/immunology , CD4-Positive T-Lymphocytes*/drug effects , CD4-Positive T-Lymphocytes*/metabolism , Lymphocyte Activation*/drug effects , Staphylococcal Infections*/drug therapy , Staphylococcal Infections*/immunology , Staphylococcal Infections*/microbiology, Animals ; Mice ; Enterotoxins ; Staphylococcus aureus/drug effects ; Cytokines/metabolism ; CD8-Positive T-Lymphocytes/drug effects ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Mice, Inbred C57BL ; Female ; Disease Models, Animal ; Superantigens/immunology |
مستخلص: | Staphylococcal toxic shock syndrome (STSS) is a rare, yet potentially fatal disease caused by Staphylococcus aureus ( S. aureus ) enterotoxins, known as superantigens, which trigger an intense immune response. Our previous study demonstrated the protective effect of tofacitinib against murine toxin-induced shock and a beneficial effect against S. aureus sepsis. In the current study, we examined the effects of tofacitinib on T-cell response in peripheral blood using a mouse model of enterotoxin-induced shock. Our data revealed that tofacitinib suppresses the activation of both CD4+ and CD8+ T cells in peripheral blood. Furthermore, both gene and protein levels of Th1 cytokines were downregulated by tofacitinib treatment in mice with enterotoxin-induced shock. Importantly, we demonstrated that CD4+ cells, but not CD8+ cells, are pathogenic in mice with enterotoxin-induced shock. In conclusion, our findings suggest that tofacitinib treatment suppresses CD4+ T-cell activation and Th1 response, thereby aiding in protection against staphylococcal toxic shock in mice. This insight may guide the future development of novel therapies for STSS. |
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معلومات مُعتمدة: | 523-2013-2750 & 2019-01135 Swedish Medical Research Council; ALFGBG-823941 & ALFGBG-933787 & ALFGBG-770411 Swedish state under the agreement between the Swedish Government and the county councils; 82360396 National Natural science foundation of China; SU-998178 & SU-984612 & SU-984324 & SU-998197 & SU-984331 & SU-998149 Sahlgrenska University Hospitals Research Foundations; 2023-419 Rune och Ulla Amlövs Stiftelse för Neurologisk och Reumatologisk Forskning |
فهرسة مساهمة: | Keywords: Th1 response; mouse; staphylococcal toxic shock syndrome; tofacitinib |
المشرفين على المادة: | 87LA6FU830 (tofacitinib) 0 (Piperidines) 0 (Pyrimidines) 0 (Enterotoxins) 0 (Cytokines) 0 (Superantigens) |
تواريخ الأحداث: | Date Created: 20240713 Date Completed: 20240713 Latest Revision: 20240809 |
رمز التحديث: | 20240809 |
مُعرف محوري في PubMed: | PMC11242597 |
DOI: | 10.3390/ijms25137456 |
PMID: | 39000566 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1422-0067 |
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DOI: | 10.3390/ijms25137456 |