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Immunity. 2013 Dec 12;39(6):1003-18. doi: 10.1016/j.immuni.2013.11.010.

The interleukin-1 family: back to the future.

Author information

  • 1Humanitas Clinical and Research Center, Via Manzoni 56, 20089 Rozzano, Italy.
  • 2Division of Infectious Diseases, University of Colorado School of Medicine, Aurora, CO 80045, USA; Department of Medicine, Radboud University Medical Center, Nijmegen 6500 HC, The Netherlands.
  • 3Humanitas Clinical and Research Center, Via Manzoni 56, 20089 Rozzano, Italy; BIOMETRA Department, Università degli Studi di Milano, 20133 Milano, Italy. Electronic address: alberto.mantovani@humanitasresearch.it.

Abstract

Interleukin-1 (IL-1) is a central mediator of innate immunity and inflammation. The IL-1 family includes seven ligands with agonist activity (IL-1α and IL-1β, IL-18, IL-33, IL-36α, IL-36β, IL-36γ), three receptor antagonists (IL-1Ra, IL-36Ra, IL-38), and an anti-inflammatory cytokine (IL-37). Members of the IL-1 Receptor (IL-1R) family include six receptor chains forming four signaling receptor complexes, two decoy receptors (IL-1R2, IL-18BP), and two negative regulators (TIR8 or SIGIRR, IL-1RAcPb). A tight regulation via receptor antagonists, decoy receptors, and signaling inhibitors ensures a balance between amplification of innate immunity and uncontrolled inflammation. All cells of the innate immune system express and/or are affected by IL-1 family members. Moreover, IL-1 family members play a key role in the differentiation and function of polarized innate and adaptive lymphoid cells. Here we will review the key properties of IL-1 family members, with emphasis on pathways of negative regulation and orchestration of innate and adaptive immunity.

Copyright © 2013 Elsevier Inc. All rights reserved.

PMID:
24332029
[PubMed - indexed for MEDLINE]
PMCID:
PMC3933951
Free PMC Article
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