دورية أكاديمية
Monocytes prime autoreactive T cells after myocardial infarction.
| العنوان: | Monocytes prime autoreactive T cells after myocardial infarction. |
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| المؤلفون: | DeBerge M; Department of Pathology, Northwestern University, Chicago, Illinois.; Feinberg Cardiovascular and Renal Research Institute, Northwestern University, Chicago, Illinois., Yu S; Division of Nephrology, Department of Medicine, Duke University, Durham, North Carolina., Dehn S; Department of Pathology, Northwestern University, Chicago, Illinois.; Feinberg Cardiovascular and Renal Research Institute, Northwestern University, Chicago, Illinois., Ifergan I; Department of Microbiology and Immunology, Northwestern University, Chicago, Illinois., Yeap XY; Department of Pathology, Northwestern University, Chicago, Illinois.; Feinberg Cardiovascular and Renal Research Institute, Northwestern University, Chicago, Illinois., Filipp M; Department of Pathology, Northwestern University, Chicago, Illinois.; Feinberg Cardiovascular and Renal Research Institute, Northwestern University, Chicago, Illinois., Becker A; Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.; Heart Center at Stanley Manne Research Institute at Lurie Children's Hospital, Chicago, Illinois., Luo X; Division of Nephrology, Department of Medicine, Duke University, Durham, North Carolina., Miller S; Department of Microbiology and Immunology, Northwestern University, Chicago, Illinois., Thorp EB; Department of Pathology, Northwestern University, Chicago, Illinois.; Feinberg Cardiovascular and Renal Research Institute, Northwestern University, Chicago, Illinois.; Heart Center at Stanley Manne Research Institute at Lurie Children's Hospital, Chicago, Illinois. |
| المصدر: | American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2020 Jan 01; Vol. 318 (1), pp. H116-H123. Date of Electronic Publication: 2019 Dec 06. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901228 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1539 (Electronic) Linking ISSN: 03636135 NLM ISO Abbreviation: Am J Physiol Heart Circ Physiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, Md. : American Physiological Society, |
| مواضيع طبية MeSH: | Adaptive Immunity* , Autoimmunity* , Cell Communication* , Lymphocyte Activation*, CD4-Positive T-Lymphocytes/*immunology , Monocytes/*immunology , Myocardial Infarction/*immunology , Myocardium/*immunology, Animals ; Antigens, Ly/immunology ; Antigens, Ly/metabolism ; CD4-Positive T-Lymphocytes/metabolism ; Disease Models, Animal ; Female ; Lymph Nodes/immunology ; Lymph Nodes/metabolism ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, Transgenic ; Monocytes/metabolism ; Myocardial Infarction/metabolism ; Myocardial Infarction/pathology ; Myocardial Infarction/physiopathology ; Myocardium/metabolism ; Myocardium/pathology ; Myosin Heavy Chains/immunology ; Myosin Heavy Chains/metabolism ; Signal Transduction ; Ventricular Function, Left ; Ventricular Remodeling |
| مستخلص: | In humans, loss of central tolerance for the cardiac self-antigen α-myosin heavy chain (α-MHC) leads to circulation of cardiac autoreactive T cells and renders the heart susceptible to autoimmune attack after acute myocardial infarction (MI). MI triggers profound tissue damage, releasing danger signals and self-antigen by necrotic cardiomyocytes, which lead to recruitment of inflammatory monocytes. We hypothesized that excessive inflammation by monocytes contributes to the initiation of adaptive immune responses to cardiac self-antigen. Using an experimental model of MI in α-MHC-mCherry reporter mice, which specifically express mCherry in cardiomyocytes, we detected α-MHC antigen in myeloid cells in the heart-draining mediastinal lymph node (MLN) 7 days after MI. To test whether monocytes were required for cardiac self-antigen trafficking to the MLN, we blocked monocyte recruitment with a C-C motif chemokine receptor type 2 (CCR2) antagonist or immune modifying nanoparticles (IMP). Blockade of monocyte recruitment reduced α-MHC antigen detection in the MLN after MI. Intramyocardial injection of the model antigen ovalbumin into OT-II transgenic mice demonstrated the requirement for monocytes in antigen trafficking and T-cell activation in the MLN. Finally, in nonobese diabetic mice, which are prone to postinfarction autoimmunity, blockade of monocyte recruitment reduced α-MHC-specific responses leading to improved tissue repair and ventricular function 28 days after MI. Taken together, these data support a role for monocytes in the onset of pathological cardiac autoimmunity following MI and suggest that therapeutic targeting of monocytes may mitigate postinfarction autoimmunity in humans. NEW & NOTEWORTHY Our study newly identifies a role for inflammatory monocytes in priming an autoimmune T-cell response after myocardial infarction. Select inhibition of monocyte recruitment to the infarct prevents trafficking of cardiac self-antigen and activation of cardiac myosin reactive T cells in the heart-draining lymph node. Therapeutic targeting of inflammatory monocytes may limit autoimmune responses to improve cardiac remodeling and preserve left ventricular function after myocardial infarction. |
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| معلومات مُعتمدة: | R01 AI114824 United States AI NIAID NIH HHS; R01 HL122309 United States HL NHLBI NIH HHS; R25 GM079300 United States GM NIGMS NIH HHS; F32 HL127958 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: autoimmunity; monocytes; myocardial infarction |
| المشرفين على المادة: | 0 (Antigens, Ly) 0 (Ly-6C antigen, mouse) 0 (Myh6 protein, mouse) EC 3.6.4.1 (Myosin Heavy Chains) |
| تواريخ الأحداث: | Date Created: 20191207 Date Completed: 20200511 Latest Revision: 20220524 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC6985803 |
| DOI: | 10.1152/ajpheart.00595.2019 |
| PMID: | 31809213 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1522-1539 |
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| DOI: | 10.1152/ajpheart.00595.2019 |