IKKβ primes inflammasome formation by recruiting NLRP3 to the trans-Golgi network

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

IKKβ primes inflammasome formation by recruiting NLRP3 to the trans-Golgi network. / Schmacke, Niklas A; O'Duill, Fionan; Gaidt, Moritz M; Szymanska, Inga; Kamper, Julia M; Schmid-Burgk, Jonathan L; Mädler, Sophia C; Mackens-Kiani, Timur; Kozaki, Tatsuya; Chauhan, Dhruv; Nagl, Dennis; Stafford, Che A; Harz, Hartmann; Fröhlich, Adrian L; Pinci, Francesca; Ginhoux, Florent; Beckmann, Roland; Mann, Matthias; Leonhardt, Heinrich; Hornung, Veit.

In: Immunity, Vol. 55, No. 12, 2022, p. 2271-2284.e7.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Schmacke, NA, O'Duill, F, Gaidt, MM, Szymanska, I, Kamper, JM, Schmid-Burgk, JL, Mädler, SC, Mackens-Kiani, T, Kozaki, T, Chauhan, D, Nagl, D, Stafford, CA, Harz, H, Fröhlich, AL, Pinci, F, Ginhoux, F, Beckmann, R, Mann, M, Leonhardt, H & Hornung, V 2022, 'IKKβ primes inflammasome formation by recruiting NLRP3 to the trans-Golgi network', Immunity, vol. 55, no. 12, pp. 2271-2284.e7. https://doi.org/10.1016/j.immuni.2022.10.021

APA

Schmacke, N. A., O'Duill, F., Gaidt, M. M., Szymanska, I., Kamper, J. M., Schmid-Burgk, J. L., Mädler, S. C., Mackens-Kiani, T., Kozaki, T., Chauhan, D., Nagl, D., Stafford, C. A., Harz, H., Fröhlich, A. L., Pinci, F., Ginhoux, F., Beckmann, R., Mann, M., Leonhardt, H., & Hornung, V. (2022). IKKβ primes inflammasome formation by recruiting NLRP3 to the trans-Golgi network. Immunity, 55(12), 2271-2284.e7. https://doi.org/10.1016/j.immuni.2022.10.021

Vancouver

Schmacke NA, O'Duill F, Gaidt MM, Szymanska I, Kamper JM, Schmid-Burgk JL et al. IKKβ primes inflammasome formation by recruiting NLRP3 to the trans-Golgi network. Immunity. 2022;55(12):2271-2284.e7. https://doi.org/10.1016/j.immuni.2022.10.021

Author

Schmacke, Niklas A ; O'Duill, Fionan ; Gaidt, Moritz M ; Szymanska, Inga ; Kamper, Julia M ; Schmid-Burgk, Jonathan L ; Mädler, Sophia C ; Mackens-Kiani, Timur ; Kozaki, Tatsuya ; Chauhan, Dhruv ; Nagl, Dennis ; Stafford, Che A ; Harz, Hartmann ; Fröhlich, Adrian L ; Pinci, Francesca ; Ginhoux, Florent ; Beckmann, Roland ; Mann, Matthias ; Leonhardt, Heinrich ; Hornung, Veit. / IKKβ primes inflammasome formation by recruiting NLRP3 to the trans-Golgi network. In: Immunity. 2022 ; Vol. 55, No. 12. pp. 2271-2284.e7.

Bibtex

@article{7a721cc31056454ab5cc4e7bf3ae1b2a,
title = "IKKβ primes inflammasome formation by recruiting NLRP3 to the trans-Golgi network",
abstract = "The NLRP3 inflammasome plays a central role in antimicrobial defense as well as in the context of sterile inflammatory conditions. NLRP3 activity is governed by two independent signals: the first signal primes NLRP3, rendering it responsive to the second signal, which then triggers inflammasome formation. Our understanding of how NLRP3 priming contributes to inflammasome activation remains limited. Here, we show that IKKβ, a kinase activated during priming, induces recruitment of NLRP3 to phosphatidylinositol-4-phosphate (PI4P), a phospholipid enriched on the trans-Golgi network. NEK7, a mitotic spindle kinase that had previously been thought to be indispensable for NLRP3 activation, was redundant for inflammasome formation when IKKβ recruited NLRP3 to PI4P. Studying iPSC-derived human macrophages revealed that the IKKβ-mediated NEK7-independent pathway constitutes the predominant NLRP3 priming mechanism in human myeloid cells. Our results suggest that PI4P binding represents a primed state into which NLRP3 is brought by IKKβ activity.",
keywords = "Mice, Animals, Humans, Inflammasomes/metabolism, NLR Family, Pyrin Domain-Containing 3 Protein/metabolism, I-kappa B Kinase, trans-Golgi Network/metabolism, NIMA-Related Kinases/metabolism, Mice, Inbred C57BL, Protein Serine-Threonine Kinases/metabolism",
author = "Schmacke, {Niklas A} and Fionan O'Duill and Gaidt, {Moritz M} and Inga Szymanska and Kamper, {Julia M} and Schmid-Burgk, {Jonathan L} and M{\"a}dler, {Sophia C} and Timur Mackens-Kiani and Tatsuya Kozaki and Dhruv Chauhan and Dennis Nagl and Stafford, {Che A} and Hartmann Harz and Fr{\"o}hlich, {Adrian L} and Francesca Pinci and Florent Ginhoux and Roland Beckmann and Matthias Mann and Heinrich Leonhardt and Veit Hornung",
note = "Copyright {\textcopyright} 2022 Elsevier Inc. All rights reserved.",
year = "2022",
doi = "10.1016/j.immuni.2022.10.021",
language = "English",
volume = "55",
pages = "2271--2284.e7",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "12",

}

RIS

TY - JOUR

T1 - IKKβ primes inflammasome formation by recruiting NLRP3 to the trans-Golgi network

AU - Schmacke, Niklas A

AU - O'Duill, Fionan

AU - Gaidt, Moritz M

AU - Szymanska, Inga

AU - Kamper, Julia M

AU - Schmid-Burgk, Jonathan L

AU - Mädler, Sophia C

AU - Mackens-Kiani, Timur

AU - Kozaki, Tatsuya

AU - Chauhan, Dhruv

AU - Nagl, Dennis

AU - Stafford, Che A

AU - Harz, Hartmann

AU - Fröhlich, Adrian L

AU - Pinci, Francesca

AU - Ginhoux, Florent

AU - Beckmann, Roland

AU - Mann, Matthias

AU - Leonhardt, Heinrich

AU - Hornung, Veit

N1 - Copyright © 2022 Elsevier Inc. All rights reserved.

PY - 2022

Y1 - 2022

N2 - The NLRP3 inflammasome plays a central role in antimicrobial defense as well as in the context of sterile inflammatory conditions. NLRP3 activity is governed by two independent signals: the first signal primes NLRP3, rendering it responsive to the second signal, which then triggers inflammasome formation. Our understanding of how NLRP3 priming contributes to inflammasome activation remains limited. Here, we show that IKKβ, a kinase activated during priming, induces recruitment of NLRP3 to phosphatidylinositol-4-phosphate (PI4P), a phospholipid enriched on the trans-Golgi network. NEK7, a mitotic spindle kinase that had previously been thought to be indispensable for NLRP3 activation, was redundant for inflammasome formation when IKKβ recruited NLRP3 to PI4P. Studying iPSC-derived human macrophages revealed that the IKKβ-mediated NEK7-independent pathway constitutes the predominant NLRP3 priming mechanism in human myeloid cells. Our results suggest that PI4P binding represents a primed state into which NLRP3 is brought by IKKβ activity.

AB - The NLRP3 inflammasome plays a central role in antimicrobial defense as well as in the context of sterile inflammatory conditions. NLRP3 activity is governed by two independent signals: the first signal primes NLRP3, rendering it responsive to the second signal, which then triggers inflammasome formation. Our understanding of how NLRP3 priming contributes to inflammasome activation remains limited. Here, we show that IKKβ, a kinase activated during priming, induces recruitment of NLRP3 to phosphatidylinositol-4-phosphate (PI4P), a phospholipid enriched on the trans-Golgi network. NEK7, a mitotic spindle kinase that had previously been thought to be indispensable for NLRP3 activation, was redundant for inflammasome formation when IKKβ recruited NLRP3 to PI4P. Studying iPSC-derived human macrophages revealed that the IKKβ-mediated NEK7-independent pathway constitutes the predominant NLRP3 priming mechanism in human myeloid cells. Our results suggest that PI4P binding represents a primed state into which NLRP3 is brought by IKKβ activity.

KW - Mice

KW - Animals

KW - Humans

KW - Inflammasomes/metabolism

KW - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism

KW - I-kappa B Kinase

KW - trans-Golgi Network/metabolism

KW - NIMA-Related Kinases/metabolism

KW - Mice, Inbred C57BL

KW - Protein Serine-Threonine Kinases/metabolism

U2 - 10.1016/j.immuni.2022.10.021

DO - 10.1016/j.immuni.2022.10.021

M3 - Journal article

C2 - 36384135

VL - 55

SP - 2271-2284.e7

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 12

ER -

ID: 331590297