Beta2-integrins in Demyelinating Disease: Not Adhering to the Paradigm

Overview

Journal J Leukoc Biol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 2009 Dec 17

PMID 20007244

Citations 16

Authors

Xianzhen Hu

Jillian E Wohler

Kari J Dugger

Scott R Barnum

Affiliations

Soon will be listed here.

Abstract

The beta(2)-integrins are a subfamily of integrins expressed on leukocytes that play an essential role in leukocyte trafficking, activation, and many other functions. Studies in EAE, the animal model for multiple sclerosis, show differential requirements for beta(2)-integrins in this disease model, ranging from critical in the case of LFA-1 (CD11a/CD18) to unimportant in the case of CD11d/CD18. Importantly, expression of beta(2)-integrins on T cell subsets provides some clues as to the function(s) these adhesion molecules play in disease development. For example, transferred EAE studies have shown that Mac-1 (CD11b/CD18) expression on alphabeta T cells is critical for disease development, and the absence of LFA-1 on Tregs in recipient mice results in exacerbated disease. In this review, we summarize recent findings regarding the role of beta(2)-integrins in demyelinating disease and new information about the role of beta(2)-integrins with respect to alterations in Treg numbers and function. In addition, we discuss the potential for targeting beta(2)-integrins in human demyelinating disease in light of the recent animal model studies.

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References

Sojka D, Huang Y, Fowell D . Mechanisms of regulatory T-cell suppression - a diverse arsenal for a moving target. Immunology. 2008; 124(1):13-22. PMC: 2434375. DOI: 10.1111/j.1365-2567.2008.02813.x. View

Staunton D, Lupher M, Liddington R, Gallatin W . Targeting integrin structure and function in disease. Adv Immunol. 2006; 91:111-57. DOI: 10.1016/S0065-2776(06)91003-7. View

Bullard D, Hu X, Schoeb T, Axtell R, Raman C, Barnum S . Critical requirement of CD11b (Mac-1) on T cells and accessory cells for development of experimental autoimmune encephalomyelitis. J Immunol. 2005; 175(10):6327-33. DOI: 10.4049/jimmunol.175.10.6327. View

Oldenhove G, de Heusch M, Urbain-Vansanten G, Urbain J, Maliszewski C, Leo O . CD4+ CD25+ regulatory T cells control T helper cell type 1 responses to foreign antigens induced by mature dendritic cells in vivo. J Exp Med. 2003; 198(2):259-66. PMC: 2194073. DOI: 10.1084/jem.20030654. View

Huitinga I, Damoiseaux J, Dopp E, Dijkstra C . Treatment with anti-CR3 antibodies ED7 and ED8 suppresses experimental allergic encephalomyelitis in Lewis rats. Eur J Immunol. 1993; 23(3):709-15. DOI: 10.1002/eji.1830230321. View

Cannella B, Cross A, Raine C . Anti-adhesion molecule therapy in experimental autoimmune encephalomyelitis. J Neuroimmunol. 1993; 46(1-2):43-55. DOI: 10.1016/0165-5728(93)90232-n. View

Mabon P, Weaver L, Dekaban G . Inhibition of monocyte/macrophage migration to a spinal cord injury site by an antibody to the integrin alphaD: a potential new anti-inflammatory treatment. Exp Neurol. 2000; 166(1):52-64. DOI: 10.1006/exnr.2000.7488. View

Scheffold A, Murphy K, Hofer T . Competition for cytokines: T(reg) cells take all. Nat Immunol. 2007; 8(12):1285-7. DOI: 10.1038/ni1207-1285. View

Gahmberg C . Leukocyte adhesion: CD11/CD18 integrins and intercellular adhesion molecules. Curr Opin Cell Biol. 1997; 9(5):643-50. DOI: 10.1016/s0955-0674(97)80117-2. View

10.

Stassen M, Jonuleit H, Muller C, Klein M, Richter C, Bopp T . Differential regulatory capacity of CD25+ T regulatory cells and preactivated CD25+ T regulatory cells on development, functional activation, and proliferation of Th2 cells. J Immunol. 2004; 173(1):267-74. DOI: 10.4049/jimmunol.173.1.267. View

11.

Bullard D, Hu X, Adams J, Schoeb T, Barnum S . p150/95 (CD11c/CD18) expression is required for the development of experimental autoimmune encephalomyelitis. Am J Pathol. 2007; 170(6):2001-8. PMC: 1899456. DOI: 10.2353/ajpath.2007.061016. View

12.

Jorgensen S, Soelberg Sorensen P . Intravenous immunoglobulin treatment of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. J Neurol Sci. 2005; 233(1-2):61-5. DOI: 10.1016/j.jns.2005.03.005. View

13.

Schoenwaelder S, Burridge K . Bidirectional signaling between the cytoskeleton and integrins. Curr Opin Cell Biol. 1999; 11(2):274-86. DOI: 10.1016/s0955-0674(99)80037-4. View

14.

Antel J, Bar-Or A . Roles of immunoglobulins and B cells in multiple sclerosis: from pathogenesis to treatment. J Neuroimmunol. 2006; 180(1-2):3-8. DOI: 10.1016/j.jneuroim.2006.06.032. View

15.

Dugger K, Zinn K, Weaver C, Bullard D, Barnum S . Effector and suppressor roles for LFA-1 during the development of experimental autoimmune encephalomyelitis. J Neuroimmunol. 2008; 206(1-2):22-7. PMC: 2665690. DOI: 10.1016/j.jneuroim.2008.10.006. View

16.

Wiendl H, Toyka K, Rieckmann P, Gold R, Hartung H, Hohlfeld R . Basic and escalating immunomodulatory treatments in multiple sclerosis: current therapeutic recommendations. J Neurol. 2008; 255(10):1449-63. DOI: 10.1007/s00415-008-0061-1. View

17.

Noti J, Johnson A, DILLON J . Structural and functional characterization of the leukocyte integrin gene CD11d. Essential role of Sp1 and Sp3. J Biol Chem. 2000; 275(12):8959-69. DOI: 10.1074/jbc.275.12.8959. View

18.

von Andrian U, Mackay C . T-cell function and migration. Two sides of the same coin. N Engl J Med. 2000; 343(14):1020-34. DOI: 10.1056/NEJM200010053431407. View

19.

Etzioni A . Genetic etiologies of leukocyte adhesion defects. Curr Opin Immunol. 2009; 21(5):481-6. DOI: 10.1016/j.coi.2009.07.005. View

20.

Gordon E, Myers K, Dougherty J, Rosen H, Ron Y . Both anti-CD11a (LFA-1) and anti-CD11b (MAC-1) therapy delay the onset and diminish the severity of experimental autoimmune encephalomyelitis. J Neuroimmunol. 1995; 62(2):153-60. DOI: 10.1016/0165-5728(95)00120-2. View