Maladaptive innate immune training of myelopoiesis links inflammatory comorbidities

Bone marrow (BM)-mediated trained innate immunity (TII) is a state of heightened immune responsiveness of hematopoietic stem and progenitor cells (HSPC) and their myeloid progeny. We show here that maladaptive BM-mediated TII underlies inflammatory comorbidities, as exemplified by the periodontitis-...

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Veröffentlicht in:	Cell Jg. 185; H. 10; S. 1709
Hauptverfasser:	Li, Xiaofei, Wang, Hui, Yu, Xiang, Saha, Gundappa, Kalafati, Lydia, Ioannidis, Charalampos, Mitroulis, Ioannis, Netea, Mihai G, Chavakis, Triantafyllos, Hajishengallis, George
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 12.05.2022
Schlagworte:	Animals Arthritis Hematopoietic Stem Cells Immunity, Innate Mice Myelopoiesis Periodontitis arthritis comorbidities inflammation myelopoiesis periodontitis hematopoietic stem and progenitor cells epigenetic rewiring trained immunity bone marrow transplantation
ISSN:	1097-4172, 1097-4172
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Abstract	Bone marrow (BM)-mediated trained innate immunity (TII) is a state of heightened immune responsiveness of hematopoietic stem and progenitor cells (HSPC) and their myeloid progeny. We show here that maladaptive BM-mediated TII underlies inflammatory comorbidities, as exemplified by the periodontitis-arthritis axis. Experimental-periodontitis-related systemic inflammation in mice induced epigenetic rewiring of HSPC and led to sustained enhancement of production of myeloid cells with increased inflammatory preparedness. The periodontitis-induced trained phenotype was transmissible by BM transplantation to naive recipients, which exhibited increased inflammatory responsiveness and disease severity when subjected to inflammatory arthritis. IL-1 signaling in HSPC was essential for their maladaptive training by periodontitis. Therefore, maladaptive innate immune training of myelopoiesis underlies inflammatory comorbidities and may be pharmacologically targeted to treat them via a holistic approach.
AbstractList	Bone marrow (BM)-mediated trained innate immunity (TII) is a state of heightened immune responsiveness of hematopoietic stem and progenitor cells (HSPC) and their myeloid progeny. We show here that maladaptive BM-mediated TII underlies inflammatory comorbidities, as exemplified by the periodontitis-arthritis axis. Experimental-periodontitis-related systemic inflammation in mice induced epigenetic rewiring of HSPC and led to sustained enhancement of production of myeloid cells with increased inflammatory preparedness. The periodontitis-induced trained phenotype was transmissible by BM transplantation to naive recipients, which exhibited increased inflammatory responsiveness and disease severity when subjected to inflammatory arthritis. IL-1 signaling in HSPC was essential for their maladaptive training by periodontitis. Therefore, maladaptive innate immune training of myelopoiesis underlies inflammatory comorbidities and may be pharmacologically targeted to treat them via a holistic approach.Bone marrow (BM)-mediated trained innate immunity (TII) is a state of heightened immune responsiveness of hematopoietic stem and progenitor cells (HSPC) and their myeloid progeny. We show here that maladaptive BM-mediated TII underlies inflammatory comorbidities, as exemplified by the periodontitis-arthritis axis. Experimental-periodontitis-related systemic inflammation in mice induced epigenetic rewiring of HSPC and led to sustained enhancement of production of myeloid cells with increased inflammatory preparedness. The periodontitis-induced trained phenotype was transmissible by BM transplantation to naive recipients, which exhibited increased inflammatory responsiveness and disease severity when subjected to inflammatory arthritis. IL-1 signaling in HSPC was essential for their maladaptive training by periodontitis. Therefore, maladaptive innate immune training of myelopoiesis underlies inflammatory comorbidities and may be pharmacologically targeted to treat them via a holistic approach. Bone marrow (BM)-mediated trained innate immunity (TII) is a state of heightened immune responsiveness of hematopoietic stem and progenitor cells (HSPC) and their myeloid progeny. We show here that maladaptive BM-mediated TII underlies inflammatory comorbidities, as exemplified by the periodontitis-arthritis axis. Experimental-periodontitis-related systemic inflammation in mice induced epigenetic rewiring of HSPC and led to sustained enhancement of production of myeloid cells with increased inflammatory preparedness. The periodontitis-induced trained phenotype was transmissible by BM transplantation to naive recipients, which exhibited increased inflammatory responsiveness and disease severity when subjected to inflammatory arthritis. IL-1 signaling in HSPC was essential for their maladaptive training by periodontitis. Therefore, maladaptive innate immune training of myelopoiesis underlies inflammatory comorbidities and may be pharmacologically targeted to treat them via a holistic approach.
Author	Ioannidis, Charalampos Netea, Mihai G Saha, Gundappa Li, Xiaofei Yu, Xiang Mitroulis, Ioannis Chavakis, Triantafyllos Wang, Hui Hajishengallis, George Kalafati, Lydia
Author_xml	– sequence: 1 givenname: Xiaofei surname: Li fullname: Li, Xiaofei organization: Department of Basic and Translational Sciences, Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA – sequence: 2 givenname: Hui surname: Wang fullname: Wang, Hui organization: Department of Basic and Translational Sciences, Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA – sequence: 3 givenname: Xiang surname: Yu fullname: Yu, Xiang organization: Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA – sequence: 4 givenname: Gundappa surname: Saha fullname: Saha, Gundappa organization: Department of Basic and Translational Sciences, Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA – sequence: 5 givenname: Lydia surname: Kalafati fullname: Kalafati, Lydia organization: Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Technische Universität Dresden, 01307 Dresden, Germany – sequence: 6 givenname: Charalampos surname: Ioannidis fullname: Ioannidis, Charalampos organization: Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Technische Universität Dresden, 01307 Dresden, Germany – sequence: 7 givenname: Ioannis surname: Mitroulis fullname: Mitroulis, Ioannis organization: Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Technische Universität Dresden, 01307 Dresden, Germany; First Department of Internal Medicine and Department of Haematology, Democritus University of Thrace, 681 00 Alexandroupolis, Greece – sequence: 8 givenname: Mihai G surname: Netea fullname: Netea, Mihai G organization: Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen 6525 XZ, the Netherlands; Department of Immunology and Metabolism, Life and Medical Science Institute, University of Bonn, 53115 Bonn, Germany – sequence: 9 givenname: Triantafyllos surname: Chavakis fullname: Chavakis, Triantafyllos email: triantafyllos.chavakis@uniklinikum-dresden.de organization: Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Technische Universität Dresden, 01307 Dresden, Germany; Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, UK. Electronic address: triantafyllos.chavakis@uniklinikum-dresden.de – sequence: 10 givenname: George surname: Hajishengallis fullname: Hajishengallis, George email: geoh@upenn.edu organization: Department of Basic and Translational Sciences, Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: geoh@upenn.edu
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Keywords	arthritis comorbidities inflammation myelopoiesis periodontitis hematopoietic stem and progenitor cells epigenetic rewiring trained immunity bone marrow transplantation
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References	35508808 - Nat Rev Immunol. 2022 Jun;22(6):336-337. doi: 10.1038/s41577-022-00733-0 35537982 - Trends Immunol. 2022 Jun;43(6):420-422. doi: 10.1016/j.it.2022.04.005
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SubjectTerms	Animals Arthritis Hematopoietic Stem Cells Immunity, Innate Mice Myelopoiesis Periodontitis
Title	Maladaptive innate immune training of myelopoiesis links inflammatory comorbidities
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