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Science. 2016 Jun 17;352(6292):aad1210. doi: 10.1126/science.aad1210.

T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4⁺ T cells.

Author information

1
MRC Centre for Transplantation, Division of Transplant Immunology and Mucosal Biology, King's College London, London SE1 9RT, UK.
2
Laboratory of Molecular Immunology and Immunology Center, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
3
Institute for Molecular Bioscience and School of Biomedical Sciences, University of Queensland, QLD 4072, Australia.
4
Institute for Medical Microbiology and Hospital Epidemiology, Medizinische Hochschule Hannover, 30625 Hannover, Germany.
5
Pathology Core, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
6
School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.
7
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
8
Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
9
Division of Immunobiology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA.
10
Department of Infection and Immunity, University of Sheffield, Sheffield S10 2RX, UK.
11
Genomics Centre, Faculty of Life Sciences and Medicine, King's College London, London SE1 9NH, UK.
12
Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA.
13
UK National Amyloidosis Centre, Division of Medicine, University College London, Royal Free Campus, London NW3 2PF, UK.
14
Academic Department of Rheumatology, Division of Immunology, Infection and Inflammatory Diseases, King's College London, London SE1 1UL, UK.
15
Laboratory of Clinical Infectious Diseases, Inflammation and Innate Immunity Unit, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
#
Contributed equally

Abstract

The NLRP3 inflammasome controls interleukin-1β maturation in antigen-presenting cells, but a direct role for NLRP3 in human adaptive immune cells has not been described. We found that the NLRP3 inflammasome assembles in human CD4(+) T cells and initiates caspase-1-dependent interleukin-1β secretion, thereby promoting interferon-γ production and T helper 1 (T(H)1) differentiation in an autocrine fashion. NLRP3 assembly requires intracellular C5 activation and stimulation of C5a receptor 1 (C5aR1), which is negatively regulated by surface-expressed C5aR2. Aberrant NLRP3 activity in T cells affects inflammatory responses in human autoinflammatory disease and in mouse models of inflammation and infection. Our results demonstrate that NLRP3 inflammasome activity is not confined to "innate immune cells" but is an integral component of normal adaptive T(H)1 responses.

PMID:
27313051
PMCID:
PMC5015487
DOI:
10.1126/science.aad1210
[Indexed for MEDLINE]
Free PMC Article

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