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

Giuseppina Arbore; Erin E. West; Rosanne Spolski; Avril A.B. Robertson; Andreas Klos; Claudia Rheinheimer; Pavel Dutow; Trent M. Woodruff; Zu Xi Yu; Luke A. O'Neill; Rebecca C. Coll; Alan Sher; Warren J. Leonard; Jörg Köhl; Pete Monk; Matthew A. Cooper; Matthew Arno; Behdad Afzali; Helen J. Lachmann; Andrew P. Cope; Katrin D. Mayer-Barber; Claudia Kemper

doi:10.1126/science.aad1210

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

Giuseppina Arbore, Erin E. West, Rosanne Spolski, Avril A.B. Robertson, Andreas Klos, Claudia Rheinheimer, Pavel Dutow, Trent M. Woodruff, Zu Xi Yu, Luke A. O'Neill, Rebecca C. Coll, Alan Sher, Warren J. Leonard, Jörg Köhl, Pete Monk, Matthew A. Cooper, Matthew Arno, Behdad Afzali, Helen J. Lachmann, Andrew P. CopeKatrin D. Mayer-Barber, Claudia Kemper^*

^*Corresponding author for this work

Institute of Systemic Inflamation Research

177 Citations (Scopus)

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⁺ Tcells and initiates caspase-1-dependent interleukin-1β secretion, thereby promoting interferon-g production and T helper 1 (TH1) 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 Tcells 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_H1 responses.

Original language	English
Article number	aad1210
Journal	Science
Volume	352
Issue number	6292
ISSN	0036-8075
DOIs	https://doi.org/10.1126/science.aad1210
Publication status	Published - 17.06.2016

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Arbore, G., West, E. E., Spolski, R., Robertson, A. A. B., Klos, A., Rheinheimer, C., Dutow, P., Woodruff, T. M., Yu, Z. X., O'Neill, L. A., Coll, R. C., Sher, A., Leonard, W. J., Köhl, J., Monk, P., Cooper, M. A., Arno, M., Afzali, B., Lachmann, H. J., ... Kemper, C. (2016). T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4+ T cells. Science, 352(6292), Article aad1210. https://doi.org/10.1126/science.aad1210

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title = "T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4+ T cells",

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+ Tcells and initiates caspase-1-dependent interleukin-1β secretion, thereby promoting interferon-g production and T helper 1 (TH1) 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 Tcells 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 TH1 responses.",

author = "Giuseppina Arbore and West, {Erin E.} and Rosanne Spolski and Robertson, {Avril A.B.} and Andreas Klos and Claudia Rheinheimer and Pavel Dutow and Woodruff, {Trent M.} and Yu, {Zu Xi} and O'Neill, {Luke A.} and Coll, {Rebecca C.} and Alan Sher and Leonard, {Warren J.} and J{\"o}rg K{\"o}hl and Pete Monk and Cooper, {Matthew A.} and Matthew Arno and Behdad Afzali and Lachmann, {Helen J.} and Cope, {Andrew P.} and Mayer-Barber, {Katrin D.} and Claudia Kemper",

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doi = "10.1126/science.aad1210",

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Arbore, G, West, EE, Spolski, R, Robertson, AAB, Klos, A, Rheinheimer, C, Dutow, P, Woodruff, TM, Yu, ZX, O'Neill, LA, Coll, RC, Sher, A, Leonard, WJ, Köhl, J, Monk, P, Cooper, MA, Arno, M, Afzali, B, Lachmann, HJ, Cope, AP, Mayer-Barber, KD & Kemper, C 2016, 'T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4+ T cells', Science, vol. 352, no. 6292, aad1210. https://doi.org/10.1126/science.aad1210

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T1 - T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4+ T cells

AU - Arbore, Giuseppina

AU - West, Erin E.

AU - Spolski, Rosanne

AU - Robertson, Avril A.B.

AU - Klos, Andreas

AU - Rheinheimer, Claudia

AU - Dutow, Pavel

AU - Woodruff, Trent M.

AU - Yu, Zu Xi

AU - O'Neill, Luke A.

AU - Coll, Rebecca C.

AU - Sher, Alan

AU - Leonard, Warren J.

AU - Köhl, Jörg

AU - Monk, Pete

AU - Cooper, Matthew A.

AU - Arno, Matthew

AU - Afzali, Behdad

AU - Lachmann, Helen J.

AU - Cope, Andrew P.

AU - Mayer-Barber, Katrin D.

AU - Kemper, Claudia

PY - 2016/6/17

Y1 - 2016/6/17

N2 - 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+ Tcells and initiates caspase-1-dependent interleukin-1β secretion, thereby promoting interferon-g production and T helper 1 (TH1) 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 Tcells 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 TH1 responses.

AB - 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+ Tcells and initiates caspase-1-dependent interleukin-1β secretion, thereby promoting interferon-g production and T helper 1 (TH1) 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 Tcells 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 TH1 responses.

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SN - 0036-8075

VL - 352

JO - Science

JF - Science

IS - 6292

M1 - aad1210

ER -

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

Abstract

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