CD95-Ligand on Peripheral Myeloid Cells Activates Syk Kinase to Trigger Their Recruitment to the Inflammatory Site

Elisabeth Letellier; Sachin Kumar; Ignacio Sancho-Martinez; Stefanie Krauth; Anne Funke-Kaiser; Sabrina Laudenklos; Katrin Konecki; Stefan Klussmann; Nina S Corsini; Susanne Kleber; Natalia Drost; Andreas Neumann; Matthieu Lévi-Strauss; Benedikt Brors; Norbert Gretz; Lutz Edler; Carmen Fischer; Oliver Hill; Meinolf Thiemann; Bahram Biglari; Saoussen Karray; Ana Martin-Villalba

doi:10.1016/j.immuni.2010.01.011

CD95-Ligand on Peripheral Myeloid Cells Activates Syk Kinase to Trigger Their Recruitment to the Inflammatory Site

Elisabeth Letellier, Sachin Kumar, Ignacio Sancho-Martinez, Stefanie Krauth, Anne Funke-Kaiser, Sabrina Laudenklos, Katrin Konecki, Stefan Klussmann, Nina S Corsini, Susanne Kleber, Natalia Drost, Andreas Neumann, Matthieu Lévi-Strauss, Benedikt Brors, Norbert Gretz, Lutz Edler, Carmen Fischer, Oliver Hill, Meinolf Thiemann, Bahram BiglariSaoussen Karray, Ana Martin-Villalba

Centre for Stem Cells & Regenerative Medicine

Research output: Contribution to journal › Article › peer-review

108 Citations (Scopus)

Abstract

Injury to the central nervous system initiates an uncontrolled inflammatory response that results in both tissue repair and destruction. Here, we showed that, in rodents and humans, injury to the spinal cord triggered surface expression of CD95 ligand (CD95L, FasL) on peripheral blood myeloid cells. CD95L stimulation of CD95 on these cells activated phosphoinositide 3-kinase (PI3K) and metalloproteinase-9 (MMP-9) via recruitment and activation of Syk kinase, ultimately leading to increased migration. Exclusive CD95L deletion in myeloid cells greatly decreased the number of neutrophils and macrophages infiltrating the injured spinal cord or the inflamed peritoneum after thioglycollate injection. Importantly, deletion of myeloid CD95L, but not of CD95 on neural cells, led to functional recovery of spinal injured animals. Our results indicate that CD95L acts on peripheral myeloid cells to induce tissue damage. Thus, neutralization of CD95L should be considered as a means to create a controlled beneficial inflammatory response.

Original language	English
Pages (from-to)	240-52
Number of pages	13
Journal	Immunity
Volume	32
Issue number	2
DOIs	https://doi.org/10.1016/j.immuni.2010.01.011
Publication status	Published - 26 Feb 2010

Keywords

Animals
Cell Movement
Cells, Cultured
Fas Ligand Protein
Humans
Inflammation
Intracellular Signaling Peptides and Proteins
Matrix Metalloproteinase 9
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Cells
Peritoneum
Peritonitis
Phosphatidylinositol 3-Kinases
Protein-Tyrosine Kinases
Signal Transduction
Spinal Cord
Thioglycolates

UN SDGs

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

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10.1016/j.immuni.2010.01.011

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Letellier, E., Kumar, S., Sancho-Martinez, I., Krauth, S., Funke-Kaiser, A., Laudenklos, S., Konecki, K., Klussmann, S., Corsini, N. S., Kleber, S., Drost, N., Neumann, A., Lévi-Strauss, M., Brors, B., Gretz, N., Edler, L., Fischer, C., Hill, O., Thiemann, M., ... Martin-Villalba, A. (2010). CD95-Ligand on Peripheral Myeloid Cells Activates Syk Kinase to Trigger Their Recruitment to the Inflammatory Site. Immunity, 32(2), 240-52. https://doi.org/10.1016/j.immuni.2010.01.011

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title = "CD95-Ligand on Peripheral Myeloid Cells Activates Syk Kinase to Trigger Their Recruitment to the Inflammatory Site",

abstract = "Injury to the central nervous system initiates an uncontrolled inflammatory response that results in both tissue repair and destruction. Here, we showed that, in rodents and humans, injury to the spinal cord triggered surface expression of CD95 ligand (CD95L, FasL) on peripheral blood myeloid cells. CD95L stimulation of CD95 on these cells activated phosphoinositide 3-kinase (PI3K) and metalloproteinase-9 (MMP-9) via recruitment and activation of Syk kinase, ultimately leading to increased migration. Exclusive CD95L deletion in myeloid cells greatly decreased the number of neutrophils and macrophages infiltrating the injured spinal cord or the inflamed peritoneum after thioglycollate injection. Importantly, deletion of myeloid CD95L, but not of CD95 on neural cells, led to functional recovery of spinal injured animals. Our results indicate that CD95L acts on peripheral myeloid cells to induce tissue damage. Thus, neutralization of CD95L should be considered as a means to create a controlled beneficial inflammatory response.",

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author = "Elisabeth Letellier and Sachin Kumar and Ignacio Sancho-Martinez and Stefanie Krauth and Anne Funke-Kaiser and Sabrina Laudenklos and Katrin Konecki and Stefan Klussmann and Corsini, {Nina S} and Susanne Kleber and Natalia Drost and Andreas Neumann and Matthieu L{\'e}vi-Strauss and Benedikt Brors and Norbert Gretz and Lutz Edler and Carmen Fischer and Oliver Hill and Meinolf Thiemann and Bahram Biglari and Saoussen Karray and Ana Martin-Villalba",

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Letellier, E, Kumar, S, Sancho-Martinez, I, Krauth, S, Funke-Kaiser, A, Laudenklos, S, Konecki, K, Klussmann, S, Corsini, NS, Kleber, S, Drost, N, Neumann, A, Lévi-Strauss, M, Brors, B, Gretz, N, Edler, L, Fischer, C, Hill, O, Thiemann, M, Biglari, B, Karray, S & Martin-Villalba, A 2010, 'CD95-Ligand on Peripheral Myeloid Cells Activates Syk Kinase to Trigger Their Recruitment to the Inflammatory Site', Immunity, vol. 32, no. 2, pp. 240-52. https://doi.org/10.1016/j.immuni.2010.01.011

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T1 - CD95-Ligand on Peripheral Myeloid Cells Activates Syk Kinase to Trigger Their Recruitment to the Inflammatory Site

AU - Letellier, Elisabeth

AU - Kumar, Sachin

AU - Sancho-Martinez, Ignacio

AU - Krauth, Stefanie

AU - Funke-Kaiser, Anne

AU - Laudenklos, Sabrina

AU - Konecki, Katrin

AU - Klussmann, Stefan

AU - Corsini, Nina S

AU - Kleber, Susanne

AU - Drost, Natalia

AU - Neumann, Andreas

AU - Lévi-Strauss, Matthieu

AU - Brors, Benedikt

AU - Gretz, Norbert

AU - Edler, Lutz

AU - Fischer, Carmen

AU - Hill, Oliver

AU - Thiemann, Meinolf

AU - Biglari, Bahram

AU - Karray, Saoussen

AU - Martin-Villalba, Ana

PY - 2010/2/26

Y1 - 2010/2/26

N2 - Injury to the central nervous system initiates an uncontrolled inflammatory response that results in both tissue repair and destruction. Here, we showed that, in rodents and humans, injury to the spinal cord triggered surface expression of CD95 ligand (CD95L, FasL) on peripheral blood myeloid cells. CD95L stimulation of CD95 on these cells activated phosphoinositide 3-kinase (PI3K) and metalloproteinase-9 (MMP-9) via recruitment and activation of Syk kinase, ultimately leading to increased migration. Exclusive CD95L deletion in myeloid cells greatly decreased the number of neutrophils and macrophages infiltrating the injured spinal cord or the inflamed peritoneum after thioglycollate injection. Importantly, deletion of myeloid CD95L, but not of CD95 on neural cells, led to functional recovery of spinal injured animals. Our results indicate that CD95L acts on peripheral myeloid cells to induce tissue damage. Thus, neutralization of CD95L should be considered as a means to create a controlled beneficial inflammatory response.

AB - Injury to the central nervous system initiates an uncontrolled inflammatory response that results in both tissue repair and destruction. Here, we showed that, in rodents and humans, injury to the spinal cord triggered surface expression of CD95 ligand (CD95L, FasL) on peripheral blood myeloid cells. CD95L stimulation of CD95 on these cells activated phosphoinositide 3-kinase (PI3K) and metalloproteinase-9 (MMP-9) via recruitment and activation of Syk kinase, ultimately leading to increased migration. Exclusive CD95L deletion in myeloid cells greatly decreased the number of neutrophils and macrophages infiltrating the injured spinal cord or the inflamed peritoneum after thioglycollate injection. Importantly, deletion of myeloid CD95L, but not of CD95 on neural cells, led to functional recovery of spinal injured animals. Our results indicate that CD95L acts on peripheral myeloid cells to induce tissue damage. Thus, neutralization of CD95L should be considered as a means to create a controlled beneficial inflammatory response.

KW - Animals

KW - Cell Movement

KW - Cells, Cultured

KW - Fas Ligand Protein

KW - Humans

KW - Inflammation

KW - Intracellular Signaling Peptides and Proteins

KW - Matrix Metalloproteinase 9

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Myeloid Cells

KW - Peritoneum

KW - Peritonitis

KW - Phosphatidylinositol 3-Kinases

KW - Protein-Tyrosine Kinases

KW - Signal Transduction

KW - Spinal Cord

KW - Thioglycolates

U2 - 10.1016/j.immuni.2010.01.011

DO - 10.1016/j.immuni.2010.01.011

M3 - Article

C2 - 20153221

SN - 1074-7613

VL - 32

SP - 240

EP - 252

JO - Immunity

JF - Immunity

IS - 2

ER -

CD95-Ligand on Peripheral Myeloid Cells Activates Syk Kinase to Trigger Their Recruitment to the Inflammatory Site

Abstract

Keywords

UN SDGs

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