XIAP Restricts TNF- and RIP3-Dependent Cell Death and Inflammasome Activation

Monica Yabal; Nicole Müller; Heiko Adler; Nathalie Knies; Christina J Groß; Rune Busk Damgaard; Hirokazu Kanegane; Marc Ringelhan; Thomas Kaufmann; Mathias Heikenwälder; Andreas Strasser; Olaf Groß; Jürgen Ruland; Christian Peschel; Mads Gyrd-Hansen; Philipp J Jost

doi:10.1016/j.celrep.2014.05.008

XIAP Restricts TNF- and RIP3-Dependent Cell Death and Inflammasome Activation

Monica Yabal, Nicole Müller, Heiko Adler, Nathalie Knies, Christina J Groß, Rune Busk Damgaard, Hirokazu Kanegane, Marc Ringelhan, Thomas Kaufmann, Mathias Heikenwälder, Andreas Strasser, Olaf Groß, Jürgen Ruland, Christian Peschel, Mads Gyrd-Hansen, Philipp J Jost

Novo Nordisk Foundation Center for Protein Research

147 Citations (Scopus)

Abstract

X-linked inhibitor of apoptosis protein (XIAP) has been identified as a potent regulator of innate immune responses, and loss-of-function mutations in XIAP cause the development of the X-linked lymphoproliferative syndrome type 2 (XLP-2) in humans. Using gene-targeted mice, we show that loss of XIAP or deletion of its RING domain lead to excessive cell death and IL-1β secretion from dendritic cells triggered by diverse Toll-like receptor stimuli. Aberrant IL-1β secretion is TNF dependent and requires RIP3 but is independent of cIAP1/cIAP2. The observed cell death also requires TNF and RIP3 but proceeds independently of caspase-1/caspase-11 or caspase-8 function. Loss of XIAP results in aberrantly elevated ubiquitylation of RIP1 outside of TNFR complex I. Virally infected Xiap(-/-) mice present with symptoms reminiscent of XLP-2. Our data show that XIAP controls RIP3-dependent cell death and IL-1β secretion in response to TNF, which might contribute to hyperinflammation in patients with XLP-2.

Original language	English
Journal	Cell Reports
Volume	7
Issue number	6
Pages (from-to)	1796-1808
ISSN	2211-1247
DOIs	https://doi.org/10.1016/j.celrep.2014.05.008
Publication status	Published - 26 Jun 2014

Access to Document

10.1016/j.celrep.2014.05.008

Cite this

Yabal, M., Müller, N., Adler, H., Knies, N., Groß, C. J., Damgaard, R. B., Kanegane, H., Ringelhan, M., Kaufmann, T., Heikenwälder, M., Strasser, A., Groß, O., Ruland, J., Peschel, C., Gyrd-Hansen, M., & Jost, P. J. (2014). XIAP Restricts TNF- and RIP3-Dependent Cell Death and Inflammasome Activation. Cell Reports, 7(6), 1796-1808. https://doi.org/10.1016/j.celrep.2014.05.008

Yabal, M, Müller, N, Adler, H, Knies, N, Groß, CJ, Damgaard, RB, Kanegane, H, Ringelhan, M, Kaufmann, T, Heikenwälder, M, Strasser, A, Groß, O, Ruland, J, Peschel, C, Gyrd-Hansen, M & Jost, PJ 2014, 'XIAP Restricts TNF- and RIP3-Dependent Cell Death and Inflammasome Activation', Cell Reports, vol. 7, no. 6, pp. 1796-1808. https://doi.org/10.1016/j.celrep.2014.05.008

@article{e6aa15edcf344db587a2e1d94b1b68ba,

title = "XIAP Restricts TNF- and RIP3-Dependent Cell Death and Inflammasome Activation",

abstract = "X-linked inhibitor of apoptosis protein (XIAP) has been identified as a potent regulator of innate immune responses, and loss-of-function mutations in XIAP cause the development of the X-linked lymphoproliferative syndrome type 2 (XLP-2) in humans. Using gene-targeted mice, we show that loss of XIAP or deletion of its RING domain lead to excessive cell death and IL-1β secretion from dendritic cells triggered by diverse Toll-like receptor stimuli. Aberrant IL-1β secretion is TNF dependent and requires RIP3 but is independent of cIAP1/cIAP2. The observed cell death also requires TNF and RIP3 but proceeds independently of caspase-1/caspase-11 or caspase-8 function. Loss of XIAP results in aberrantly elevated ubiquitylation of RIP1 outside of TNFR complex I. Virally infected Xiap(-/-) mice present with symptoms reminiscent of XLP-2. Our data show that XIAP controls RIP3-dependent cell death and IL-1β secretion in response to TNF, which might contribute to hyperinflammation in patients with XLP-2.",

author = "Monica Yabal and Nicole M{\"u}ller and Heiko Adler and Nathalie Knies and Gro{\ss}, {Christina J} and Damgaard, {Rune Busk} and Hirokazu Kanegane and Marc Ringelhan and Thomas Kaufmann and Mathias Heikenw{\"a}lder and Andreas Strasser and Olaf Gro{\ss} and J{\"u}rgen Ruland and Christian Peschel and Mads Gyrd-Hansen and Jost, {Philipp J}",

year = "2014",

month = jun,

day = "26",

doi = "10.1016/j.celrep.2014.05.008",

language = "English",

volume = "7",

pages = "1796--1808",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - XIAP Restricts TNF- and RIP3-Dependent Cell Death and Inflammasome Activation

AU - Yabal, Monica

AU - Müller, Nicole

AU - Adler, Heiko

AU - Knies, Nathalie

AU - Groß, Christina J

AU - Damgaard, Rune Busk

AU - Kanegane, Hirokazu

AU - Ringelhan, Marc

AU - Kaufmann, Thomas

AU - Heikenwälder, Mathias

AU - Strasser, Andreas

AU - Groß, Olaf

AU - Ruland, Jürgen

AU - Peschel, Christian

AU - Gyrd-Hansen, Mads

AU - Jost, Philipp J

PY - 2014/6/26

Y1 - 2014/6/26

N2 - X-linked inhibitor of apoptosis protein (XIAP) has been identified as a potent regulator of innate immune responses, and loss-of-function mutations in XIAP cause the development of the X-linked lymphoproliferative syndrome type 2 (XLP-2) in humans. Using gene-targeted mice, we show that loss of XIAP or deletion of its RING domain lead to excessive cell death and IL-1β secretion from dendritic cells triggered by diverse Toll-like receptor stimuli. Aberrant IL-1β secretion is TNF dependent and requires RIP3 but is independent of cIAP1/cIAP2. The observed cell death also requires TNF and RIP3 but proceeds independently of caspase-1/caspase-11 or caspase-8 function. Loss of XIAP results in aberrantly elevated ubiquitylation of RIP1 outside of TNFR complex I. Virally infected Xiap(-/-) mice present with symptoms reminiscent of XLP-2. Our data show that XIAP controls RIP3-dependent cell death and IL-1β secretion in response to TNF, which might contribute to hyperinflammation in patients with XLP-2.

AB - X-linked inhibitor of apoptosis protein (XIAP) has been identified as a potent regulator of innate immune responses, and loss-of-function mutations in XIAP cause the development of the X-linked lymphoproliferative syndrome type 2 (XLP-2) in humans. Using gene-targeted mice, we show that loss of XIAP or deletion of its RING domain lead to excessive cell death and IL-1β secretion from dendritic cells triggered by diverse Toll-like receptor stimuli. Aberrant IL-1β secretion is TNF dependent and requires RIP3 but is independent of cIAP1/cIAP2. The observed cell death also requires TNF and RIP3 but proceeds independently of caspase-1/caspase-11 or caspase-8 function. Loss of XIAP results in aberrantly elevated ubiquitylation of RIP1 outside of TNFR complex I. Virally infected Xiap(-/-) mice present with symptoms reminiscent of XLP-2. Our data show that XIAP controls RIP3-dependent cell death and IL-1β secretion in response to TNF, which might contribute to hyperinflammation in patients with XLP-2.

U2 - 10.1016/j.celrep.2014.05.008

DO - 10.1016/j.celrep.2014.05.008

M3 - Journal article

C2 - 24882010

SN - 2211-1247

VL - 7

SP - 1796

EP - 1808

JO - Cell Reports

JF - Cell Reports

IS - 6

ER -

XIAP Restricts TNF- and RIP3-Dependent Cell Death and Inflammasome Activation

Abstract

Access to Document

Fingerprint

Cite this