Journal
IMMUNITY
Volume 39, Issue 6, Pages 1003-1018Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2013.11.010
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Funding
- European Research Council
- European Commission [FP7-HEALTH-2011-ADITEC 280873]
- Associazione Italiana per la Ricerca sul Cancro (AIRC)
- National Institutes of Health [A115614, AR-45584]
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Interleukin-1 (IL-1) is a central mediator of innate immunity and inflammation. The IL-1 family includes seven ligands with agonist activity (IL-1 alpha and IL-1 beta, IL-18, IL-33, IL-36 alpha, IL-36 beta, IL-36 gamma), 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.
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