Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system

Romain Cayrol; Karolina Wosik; Jennifer L. Berard; Aurore Dodelet-Devillers; Igal Ifergan; Hania Kebir; Arsalan S. Haqqani; Katharina Kreymborg; Sebastian Krug; Robert Moumdjian; Alain Bouthillier; Burkhard Becher; Nathalie Arbour; Samuel David; Danica Stanimirovic; Alexandre Prat

doi:10.1038/ni1551

Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system

Romain Cayrol, Karolina Wosik, Jennifer L. Berard, Aurore Dodelet-Devillers, Igal Ifergan, Hania Kebir, Arsalan S. Haqqani, Katharina Kreymborg, Sebastian Krug, Robert Moumdjian, Alain Bouthillier, Burkhard Becher, Nathalie Arbour, Samuel David, Danica Stanimirovic, Alexandre Prat^*

^*Corresponding author for this work

Microbiology-Immunology

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

367 Scopus citations

Abstract

Adhesion molecules of the immunoglobulin superfamily are crucial effectors of leukocyte trafficking into the central nervous system. Using a lipid raft-based proteomic approach, we identified ALCAM as an adhesion molecule involved in leukocyte migration across the blood-brain barrier (BBB). ALCAM expressed on BBB endothelium localized together with CD6 on leukocytes and with BBB endothelium transmigratory cups. ALCAM expression on BBB cells was upregulated in active multiple sclerosis and experimental autoimmune encephalomyelitis lesions. Moreover, ALCAM blockade restricted the transmigration of CD4⁺ lymphocytes and monocytes across BBB endothelium in vitro and in vivo and reduced the severity and delayed the time of onset of experimental autoimmune encephalomyelitis. Our findings indicate an important function for ALCAM in the recruitment of leukocytes into the brain and identify ALCAM as a potential target for the therapeutic dampening of neuroinflammation.

Original language	English (US)
Pages (from-to)	137-145
Number of pages	9
Journal	Nature Immunology
Volume	9
Issue number	2
DOIs	https://doi.org/10.1038/ni1551
State	Published - Feb 2008

Funding

We thank M. Bernard and J. Laganière for technical assistance in the laboratory; C. Gaspar for critical reading of the manuscript; and J.P. Antel for human material and intellectual input. Supported by the Canadian Institutes of Health Research (Neuroscience Mental Health and Addiction; MOP-81088; Neuroinflammation training program, R.C., J.L.B., A.D.-D. and S.K.; and Senior Research Fellowship Phase 2, N.A.), the Multiple Sclerosis Society of Canada (A.P., R.C., J.L.B., A.D.-D., K.W., H.K. and I.I.), the Canadian Foundation for Innovation, the US National Multiple Sclerosis Society (B.B.), the Swiss National Science Foundation (B.B.), Fonds de la Recherche en Santé du Québec (A.P.), and the Center for Neuroscience in Zurich (K.K.).

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Cayrol, R., Wosik, K., Berard, J. L., Dodelet-Devillers, A., Ifergan, I., Kebir, H., Haqqani, A. S., Kreymborg, K., Krug, S., Moumdjian, R., Bouthillier, A., Becher, B., Arbour, N., David, S., Stanimirovic, D., & Prat, A. (2008). Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system. Nature Immunology, 9(2), 137-145. https://doi.org/10.1038/ni1551

@article{9330e0dfeb5a43699a191d50e7c807c0,

title = "Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system",

abstract = "Adhesion molecules of the immunoglobulin superfamily are crucial effectors of leukocyte trafficking into the central nervous system. Using a lipid raft-based proteomic approach, we identified ALCAM as an adhesion molecule involved in leukocyte migration across the blood-brain barrier (BBB). ALCAM expressed on BBB endothelium localized together with CD6 on leukocytes and with BBB endothelium transmigratory cups. ALCAM expression on BBB cells was upregulated in active multiple sclerosis and experimental autoimmune encephalomyelitis lesions. Moreover, ALCAM blockade restricted the transmigration of CD4+ lymphocytes and monocytes across BBB endothelium in vitro and in vivo and reduced the severity and delayed the time of onset of experimental autoimmune encephalomyelitis. Our findings indicate an important function for ALCAM in the recruitment of leukocytes into the brain and identify ALCAM as a potential target for the therapeutic dampening of neuroinflammation.",

author = "Romain Cayrol and Karolina Wosik and Berard, {Jennifer L.} and Aurore Dodelet-Devillers and Igal Ifergan and Hania Kebir and Haqqani, {Arsalan S.} and Katharina Kreymborg and Sebastian Krug and Robert Moumdjian and Alain Bouthillier and Burkhard Becher and Nathalie Arbour and Samuel David and Danica Stanimirovic and Alexandre Prat",

note = "Funding Information: We thank M. Bernard and J. Lagani{\`e}re for technical assistance in the laboratory; C. Gaspar for critical reading of the manuscript; and J.P. Antel for human material and intellectual input. Supported by the Canadian Institutes of Health Research (Neuroscience Mental Health and Addiction; MOP-81088; Neuroinflammation training program, R.C., J.L.B., A.D.-D. and S.K.; and Senior Research Fellowship Phase 2, N.A.), the Multiple Sclerosis Society of Canada (A.P., R.C., J.L.B., A.D.-D., K.W., H.K. and I.I.), the Canadian Foundation for Innovation, the US National Multiple Sclerosis Society (B.B.), the Swiss National Science Foundation (B.B.), Fonds de la Recherche en Sant{\'e} du Qu{\'e}bec (A.P.), and the Center for Neuroscience in Zurich (K.K.).",

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Cayrol, R, Wosik, K, Berard, JL, Dodelet-Devillers, A, Ifergan, I, Kebir, H, Haqqani, AS, Kreymborg, K, Krug, S, Moumdjian, R, Bouthillier, A, Becher, B, Arbour, N, David, S, Stanimirovic, D & Prat, A 2008, 'Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system', Nature Immunology, vol. 9, no. 2, pp. 137-145. https://doi.org/10.1038/ni1551

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AU - Wosik, Karolina

AU - Berard, Jennifer L.

AU - Dodelet-Devillers, Aurore

AU - Ifergan, Igal

AU - Kebir, Hania

AU - Haqqani, Arsalan S.

AU - Kreymborg, Katharina

AU - Krug, Sebastian

AU - Moumdjian, Robert

AU - Bouthillier, Alain

AU - Becher, Burkhard

AU - Arbour, Nathalie

AU - David, Samuel

AU - Stanimirovic, Danica

AU - Prat, Alexandre

N1 - Funding Information: We thank M. Bernard and J. Laganière for technical assistance in the laboratory; C. Gaspar for critical reading of the manuscript; and J.P. Antel for human material and intellectual input. Supported by the Canadian Institutes of Health Research (Neuroscience Mental Health and Addiction; MOP-81088; Neuroinflammation training program, R.C., J.L.B., A.D.-D. and S.K.; and Senior Research Fellowship Phase 2, N.A.), the Multiple Sclerosis Society of Canada (A.P., R.C., J.L.B., A.D.-D., K.W., H.K. and I.I.), the Canadian Foundation for Innovation, the US National Multiple Sclerosis Society (B.B.), the Swiss National Science Foundation (B.B.), Fonds de la Recherche en Santé du Québec (A.P.), and the Center for Neuroscience in Zurich (K.K.).

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Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system

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