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Journal articles
Activated leukocyte cell adhesion molecule regulates B lymphocyte migration across central nervous system barriers
L. Michel
1, 2
C. Grasmuck
3
M. Charabati
3
M.-A. Lécuyer
3
S. Zandee
3
T. Dhaeze
3
J.I. Alvarez
3
R. Li
4
S. Larouche
3
L. Bourbonnière
3
R. Moumdjian
3
A. Bouthillier
3
B. Lahav
3
P. Duquette
3
A. Bar-Or
4
J.L. Gommerman
5
E. Peelen
3
A. Prat
3
1
MICMAC - Microenvironment, Cell Differentiation, Immunology and Cancer (INSERM UMR1236, Campus Santé, Bât 2, Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France - France)
- UR1 - Université de Rennes 1 (2 rue du Thabor - CS 46510 - 35065 Rennes cedex - France)
- UNIV-RENNES - Université de Rennes (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1236 (101, rue de Tolbiac, 75013 Paris - France)
- Biosit : Biologie - Santé - Innovation Technologique - Structure Fédérative de Recherche en Biologie et Santé de Rennes (Université Rennes 1 - Campus Santé Villejean - 2, avenue Professeur Léon Bernard 35043 Rennes cedex - France)
2
CIC - Centre d'Investigation Clinique [Rennes] (Rue Henri Le Guilloux - Pavillon Clémenceau 35033 Rennes Cedex 9 - France)
- UR1 - Université de Rennes 1 (2 rue du Thabor - CS 46510 - 35065 Rennes cedex - France)
- UNIV-RENNES - Université de Rennes (France)
- Hôpital Pontchaillou (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : CIC1414 (101, rue de Tolbiac, 75013 Paris - France)
3
UdeM - Université de Montréal (2900 Boulevard Edouard-Montpetit, Montréal, QC H3T 1J4 - Canada)
4
University of Pennsylvania [Philadelphia] (3451 Walnut Street, Philadelphia, PA 19104 | 215-898-5000 - United States)
5
University of Toronto (27 King's College Circle, Toronto M5S 1A1 - Canada)
Abstract : The presence of B lymphocyte-associated oligoclonal immunoglobulins in the cerebrospinal fluid is a classic hallmark of multiple sclerosis (MS). The clinical efficacy of anti-CD20 therapies supports a major role for B lymphocytes in MS development. Although activated oligoclonal populations of pathogenic B lymphocytes are able to traffic between the peripheral circulation and the central nervous system (CNS) in patients with MS, molecular players involved in this migration have not yet been elucidated. In this study, we demonstrated that activated leukocyte cell adhesion molecule (ALCAM/CD166) identifies subsets of proinflammatory B lymphocytes and drives their transmigration across different CNS barriers in mouse and human. We also showcased that blocking ALCAM alleviated disease severity in animals affected by a B cell-dependent form of experimental autoimmune encephalomyelitis. Last, we determined that the proportion of ALCAM+ B lymphocytes was increased in the peripheral blood and within brain lesions of patients with MS. Our findings indicate that restricting access to the CNS by targeting ALCAM on pathogenic B lymphocytes might represent a promising strategy for the development of next-generation B lymphocyte-targeting therapies for the treatment of MS. © 2019 The Authors.
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Journal articles
Domain :
Complete list of metadatas
https://hal-univ-rennes1.archives-ouvertes.fr/hal-02397748
Contributor : Laurent Jonchère <>
Submitted on : Friday, December 6, 2019 - 4:31:49 PM
Last modification on : Monday, July 20, 2020 - 12:34:52 PM
Contributor : Laurent Jonchère <>
Submitted on : Friday, December 6, 2019 - 4:31:49 PM
Last modification on : Monday, July 20, 2020 - 12:34:52 PM
Identifiers
- HAL Id : hal-02397748, version 1
- DOI : 10.1126/scitranslmed.aaw0475
- PUBMED : 31723036
Collections
UNIV-RENNES1 | CIC | U917 | BIOSIT | CIC203 | UR1-UFR-SVE | MICMAC | UNIV-RENNES
Citation
L. Michel, C. Grasmuck, M. Charabati, M.-A. Lécuyer, S. Zandee, et al.. Activated leukocyte cell adhesion molecule regulates B lymphocyte migration across central nervous system barriers. Science Translational Medicine, American Association for the Advancement of Science, 2019, 11 (518), pp.eaaw0475. ⟨10.1126/scitranslmed.aaw0475⟩. ⟨hal-02397748⟩
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