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Beyond canonical inflammasomes: emerging pathways in IL-1-mediated autoinflammatory disease

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Abstract

In recent years, non-communicable chronic diseases that are potentiated by sterile inflammation have replaced infectious diseases as the major threat to human health. Sterile inflammation that results from aberrant tissue damage plays pivotal roles in the pathogenesis of numerous acute and chronic inflammatory diseases including atherosclerosis, type 2 diabetes, cancer, obesity, and multiple neurodegenerative diseases. The cellular events and molecular signaling pathways that govern sterile inflammation currently remain poorly defined; however, emerging data suggest central roles for IL-1 in driving autoimmune and inflammatory disease pathogenesis. Improved characterization of the immunological pathways that contribute to sterile inflammation are desperately needed to develop effective therapeutics to treat these devastating diseases. In this review, we discuss recent advances in our understanding of how IL-1 is regulated in response to tissue damage. In particular, we highlight recent studies that describe novel roles for conventional cell death molecules in the regulation of IL-1β production.

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Abbreviations

IL:

Interleukin

PAMPs:

Pathogen-associated molecular patterns

DAMPs:

Danger-associated molecular patterns

IL-1R:

IL-1 receptor

NLR:

NOD-like receptor

ALR:

AIM2-like receptor

TLR:

Toll-like receptor

CNS:

Central nervous system

EAE:

Experimental autoimmune encephalomyelitis

ALS:

Amyotrophic lateral sclerosis

Tregs:

Regulatory T cells

IAPP:

Islet amyloid polypeptide

SLE:

Systemic lupus erythematosus

RIP:

Receptor-interacting protein

FADD:

FAS-associated death domain

TNFR1:

TNF receptor 1

IAPs:

Inhibitors of apoptosis proteins

COPD:

Chronic obstructive pulmonary disease

ER:

Endoplasmic reticulum

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Acknowledgments

We apologize to authors whose work could not be referenced in this review due to space limitations. We thank Prajwal Gurung and Si Ming Man for their helpful discussions. This work was supported by: the National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health, under Award Number AR056296 (T.-D.K); the National Cancer Institute, part of the National Institutes of Health, under Award Number CA163507 (T.-D.K); the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, under Award Number AI101935 (T.-D.K); and ALSAC.

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The authors declare no competing financial interests.

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  1. Department of Immunology, St. Jude Children’s Research Hospital, MS #351, 262 Danny Thomas Place, Suite E7004, Memphis, TN, 38105-2794, USA

    John R. Lukens & Thirumala-Devi Kanneganti

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Correspondence to Thirumala-Devi Kanneganti.

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This article is a contribution to the special issue on Mechanisms of Tissue Injury in Autoimmune Diseases - Guest Editor: Dan Eilat

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Lukens, J.R., Kanneganti, TD. Beyond canonical inflammasomes: emerging pathways in IL-1-mediated autoinflammatory disease. Semin Immunopathol 36, 595–609 (2014). https://doi.org/10.1007/s00281-014-0434-8

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