Cited by 364Immune Response and InflammationT-cell and B-cell ImmunologyCell Adhesion Molecules Research

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Tissue Homeostasis and Inflammation

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Meizlish, Matthew L., Franklin, Ruth A., Zhou, Xu, Medzhitov, Ruslan·2021·Annual Review of Immunology

DOI 10.1146/annurev-immunol-061020-053734

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Abstract

There is a growing interest in understanding tissue organization, homeostasis, and inflammation. However, despite an abundance of data, the organizing principles of tissue biology remain poorly defined. Here, we present a perspective on tissue organization based on the relationships between cell types and the functions that they perform. We provide a formal definition of tissue homeostasis as a collection of circuits that regulate specific variables within the tissue environment, and we describe how the functional organization of tissues allows for the maintenance of both tissue and systemic homeostasis. This leads to a natural definition of inflammation as a response to deviations from homeostasis that cannot be reversed by homeostatic mechanisms alone. We describe how inflammatory signals act on the same cellular functions involved in normal tissue organization and homeostasis in order to coordinate emergency responses to perturbations and ultimately return the system to a homeostatic state. Finally, we consider the hierarchy of homeostatic and inflammatory circuits and the implications for the development of inflammatory diseases.

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Authors: Meizlish, M. L., Franklin, R. A., Zhou, X., & Medzhitov, R.
Affiliations: Yale University (US)
Harvard University (US)
Boston Children's Hospital (US)
Howard Hughes Medical Institute (US)
Corresponding author: Medzhitov, Ruslan
ORCID: Meizlish, Matthew L.
Franklin, Ruth A.
Zhou, Xu
Medzhitov, Ruslan
Venue: Annual Review of Immunology
Publisher: Annual Reviews
Published: 2021-04-26
Volume: 39
Issue: 1
Pages: 557-581
ISSN: 0732-0582 (ISSN-L)
1545-3278
DOI: 10.1146/annurev-immunol-061020-053734
OpenAlex: W3135024921
Cited by: 364
References: 158
Citations by year: 2026: 53 · 2025: 88 · 2024: 95 · 2023: 72 · 2022: 44 · 2021: 11
FWCI: 5.69
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Annual Review of Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: Howard Hughes Medical Institute
Cancer Research Institute
National Institutes of Health
National Heart, Lung, and Blood Institute (HL139116, F31HL139116)
National Institute of General Medical Sciences (T32GM136651)
National Institute of Allergy and Infectious Diseases (R01AI144152)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords: tissue homeostasis, inflammation, tissue organization, systemic homeostasis, inflammatory signaling, emergency response, inflammatory diseases, cell types
MeSH terms: Animals, Homeostasis, Humans, Inflammation

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