دورية أكاديمية
أعرض في EDS

Thrombocytopenia Independently Leads to Changes in Monocyte Immune Function.

التفاصيل البيبلوغرافية
العنوان: Thrombocytopenia Independently Leads to Changes in Monocyte Immune Function.
المؤلفون: Li C; Aab Cardiovascular Research Institute (C.L., S.K.T., B.N.-L., S.K.B.-N., P.M., A.C.L., C.N.M.), University of Rochester School of Medicine and Dentistry, NY., Ture SK; Aab Cardiovascular Research Institute (C.L., S.K.T., B.N.-L., S.K.B.-N., P.M., A.C.L., C.N.M.), University of Rochester School of Medicine and Dentistry, NY., Nieves-Lopez B; Aab Cardiovascular Research Institute (C.L., S.K.T., B.N.-L., S.K.B.-N., P.M., A.C.L., C.N.M.), University of Rochester School of Medicine and Dentistry, NY.; University of Puerto Rico, Medical Sciences Campus, San Juan (B.N.-L.)., Blick-Nitko SK; Aab Cardiovascular Research Institute (C.L., S.K.T., B.N.-L., S.K.B.-N., P.M., A.C.L., C.N.M.), University of Rochester School of Medicine and Dentistry, NY., Maurya P; Aab Cardiovascular Research Institute (C.L., S.K.T., B.N.-L., S.K.B.-N., P.M., A.C.L., C.N.M.), University of Rochester School of Medicine and Dentistry, NY., Livada AC; Aab Cardiovascular Research Institute (C.L., S.K.T., B.N.-L., S.K.B.-N., P.M., A.C.L., C.N.M.), University of Rochester School of Medicine and Dentistry, NY., Stahl TJ; Genomics Research Center (T.J.S.), University of Rochester School of Medicine and Dentistry, NY., Kim M; Department of Microbiology and Immunology (M.K., C.N.M.), University of Rochester School of Medicine and Dentistry, NY., Pietropaoli AP; Department of Medicine (A.P.P., C.N.M.), University of Rochester School of Medicine and Dentistry, NY., Morrell CN; Aab Cardiovascular Research Institute (C.L., S.K.T., B.N.-L., S.K.B.-N., P.M., A.C.L., C.N.M.), University of Rochester School of Medicine and Dentistry, NY.; Department of Microbiology and Immunology (M.K., C.N.M.), University of Rochester School of Medicine and Dentistry, NY.; Department of Medicine (A.P.P., C.N.M.), University of Rochester School of Medicine and Dentistry, NY.; Department of Pathology and Laboratory Medicine (C.N.M.), University of Rochester School of Medicine and Dentistry, NY.
المصدر: Circulation research [Circ Res] 2024 Apr 12; Vol. 134 (8), pp. 970-986. Date of Electronic Publication: 2024 Mar 08.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0047103 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4571 (Electronic) Linking ISSN: 00097330 NLM ISO Abbreviation: Circ Res Subsets: MEDLINE
أسماء مطبوعة: Publication: Baltimore, MD : Lippincott Williams & Wilkins
Original Publication: Baltimore, Md. Grune & Stratton.
مواضيع طبية MeSH: Thrombocytopenia*/metabolism , Sepsis*/metabolism, Mice ; Animals ; Humans ; Monocytes/metabolism ; Blood Platelets/metabolism ; Immunity ; Platelet Activation
مستخلص: Background: While platelets have well-studied hemostatic functions, platelets are immune cells that circulate at the interface between the vascular wall and white blood cells. The physiological implications of these constant transient interactions are poorly understood. Activated platelets induce and amplify immune responses, but platelets may also maintain immune homeostasis in healthy conditions, including maintaining vascular integrity and T helper cell differentiation, meaning that platelets are central to both immune responses and immune quiescence. Clinical data have shown an association between low platelet counts (thrombocytopenia) and immune dysfunction in patients with sepsis and extracorporeal membrane oxygenation, further implicating platelets as more holistic immune regulators, but studies of platelet immune functions in nondisease contexts have had limited study.
Methods: We used in vivo models of thrombocytopenia and in vitro models of platelet and monocyte interactions, as well as RNA-seq and ATAC-seq (assay for transposase-accessible chromatin with sequencing), to mechanistically determine how resting platelet and monocyte interactions immune program monocytes.
Results: Circulating platelets and monocytes interact in a CD47-dependent manner to regulate monocyte metabolism, histone methylation, and gene expression. Resting platelet-monocyte interactions limit TLR (toll-like receptor) signaling responses in healthy conditions in an innate immune training-like manner. In both human patients with sepsis and mouse sepsis models, thrombocytopenia exacerbated monocyte immune dysfunction, including increased cytokine production.
Conclusions: Thrombocytopenia immune programs monocytes in a manner that may lead to immune dysfunction in the context of sepsis. This is the first demonstration that sterile, endogenous cell interactions between resting platelets and monocytes regulate monocyte metabolism and pathogen responses, demonstrating platelets to be immune rheostats in both health and disease.
Competing Interests: Disclosures None.
التعليقات: Update of: bioRxiv. 2023 May 12;:. (PMID: 37214993)
Comment in: Circ Res. 2024 Apr 12;134(8):987-989. (PMID: 38603477)
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معلومات مُعتمدة: R01 HL141106 United States HL NHLBI NIH HHS; R01 HL160610 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: acute coronary syndrome; chromatin assembly and disassembly; monocytes; platelet count; toll-like receptor agonists
تواريخ الأحداث: Date Created: 20240308 Date Completed: 20240415 Latest Revision: 20240505
رمز التحديث: 20240505
مُعرف محوري في PubMed: PMC11069346
DOI: 10.1161/CIRCRESAHA.123.323662
PMID: 38456277
قاعدة البيانات: MEDLINE
الوصف
تدمد:1524-4571
DOI:10.1161/CIRCRESAHA.123.323662