Immune cell entry into the central nervous system: Involvement of adhesion molecules and chemokines

Engelhardt, Britta

doi:10.1016/j.jns.2008.05.019

Cited by 156 publications

(112 citation statements)

References 27 publications

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“…This requires a series of different leukocyte adhesion molecules, including selectins (E-selectin, P-selectin) for rolling adhesion and immunoglobulin family members for firm adhesion (Huang et al 2006;Aird 2007b). The expression of these adhesion molecules is much lower in CNS ECs than in peripheral ECs but is elevated during neuroinflammatory diseases, such as stroke and MS (Henninger et al 1997;Huang et al 2006;Engelhardt 2008;Daneman et al 2010a). Interest-ingly, different subsets of inflammatory cells are observed infiltrating the CNS in different diseases.…”

Section: Leukocyte Adhesion Molecules (Lams)mentioning

confidence: 99%

The Blood–Brain Barrier

Daneman

Prat

2015

Cold Spring Harb Perspect Biol

2,401

1,829

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Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood-brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of these barrier properties are an important component of pathology and progression of different neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of the blood vessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease.

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Section: Leukocyte Adhesion Molecules (Lams)mentioning

confidence: 99%

The Blood–Brain Barrier

Daneman

Prat

2015

Cold Spring Harb Perspect Biol

2,401

1,829

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“…Although much progress has been made in understanding Tcell trafficking to the CNS (6,16), the molecular signature that permits myelin-reactive T H cells to breach the CNS barriers and infiltrate the parenchyma remains to be fully defined. Chemokine receptor expression profiles differ by T H cell subtype and, in combination with selectins and integrins, define their final destination (26,27).…”

Section: Discussionmentioning

confidence: 99%

“…There, a sequential interaction with a multitude of endothelial adhesion molecules and chemokines leads to T helper (T H ) cell migration into the CNS parenchyma. Several ligand/receptor pairs have been implicated in the pathogeneses of MS and EAE (5,6). Therefore, manipulation of molecules involved in T-cell trafficking poses an attractive opportunity for therapeutic interventions.…”

Section: Ultiple Sclerosis (Ms) Is An Immune-mediated Demyelinatingmentioning

confidence: 99%

1,25-Dihydroxyvitamin D₃selectively and reversibly impairs T helper-cell CNS localization

Grishkan

Fairchild

Calabresi

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Pharmacologic targeting of T helper (T H ) cell trafficking poses an attractive opportunity for amelioration of autoimmune diseases such as multiple sclerosis (MS). MS risk is associated with vitamin D deficiency, and its bioactive form, 1,25-dihydroxyvitamin D3 [1,25(OH) 2 D 3 ], has been shown to prevent experimental autoimmune encephalomyelitis, a mouse model of MS, via an incompletely understood mechanism. Herein, we systematically examined 1,25 (OH) 2 D 3 effects on T H cells during their migration from the lymph nodes to the CNS. Our data demonstrate that myelin-reactive T H cells are successfully generated in the presence of 1,25(OH) 2 D 3 , secrete proinflammatory cytokines, and do not preferentially differentiate into suppressor T cells. These cells are able to leave the lymph node, enter the peripheral circulation, and migrate to the s. c. immunization sites. However, T H cells from 1,25(OH) 2 D 3 -treated mice are unable to enter the CNS parenchyma but are instead maintained in the periphery. Upon treatment cessation, mice rapidly develop experimental autoimmune encephalomyelitis, demonstrating that 1,25(OH) 2 D 3 prevents the disease only temporarily likely by halting T H cell migration into the CNS. The pathogeneses of MS and EAE require localization of selfreactive T cells to the CNS. Myelin-specific effector T cells are primed in the lymph nodes (LNs) and subsequently travel a complex route and arrive at the CNS barriers. There, a sequential interaction with a multitude of endothelial adhesion molecules and chemokines leads to T helper (T H ) cell migration into the CNS parenchyma. Several ligand/receptor pairs have been implicated in the pathogeneses of MS and EAE (5, 6). Therefore, manipulation of molecules involved in T-cell trafficking poses an attractive opportunity for therapeutic interventions. Recent studies have highlighted a role for vitamin D in immune cell migration (7-10), but whether 1,25(OH) 2 D 3 affects trafficking of lymphocytes in MS and/or EAE has not been investigated.A recent study using conditional deletion of the vitamin D receptor (VDR) has demonstrated that 1,25(OH) 2 D 3 prevents EAE by acting directly on the encephalitogenic T H cells (11 (Fig. S1), were recovered from the CNS of 1,25(OH) 2 D 3 -treated mice, all of which remained disease-free ( Fig. 1 A and B). Moreover, both vehicle-and 1,25(OH) 2 D 3 -treated groups had significantly higher proportions of splenic CD4 + T cells compared with the naive control (Fig. 1B). Thus, EAE prevention is accompanied by T H cell expansion in the periphery and a complete absence of inflammatory infiltrates in the CNS of 1,25(OH) 2 D 3 -treated animals, leading us to hypothesize that 1,25 (OH) 2 D 3 affects the ability of encephalitogenic T cells to enter the CNS without interfering with their activation.1,25(OH) 2 D 3 Does Not Affect Activation of Pathogenic T H Cells. We next examined the effect of 1,25(OH) 2 D 3 on the peripheral inflammatory response following immunization (Fig. S2). An equivalent increase in the proportion...

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“…Although, some studies have suggested that P-selectin has a crucial role in the early migration of lymphocytes into the non-inflamed brain, others have suggested that there is no role of P-selectin in the migration of lymphocytes during inflammatory condition within CNS since P-selectin deficient mice also develop EAE which is indistinguishable from wildtype. 64,68,73,74,[76][77][78] The 'rolling' of lymphocytes is followed by the interaction of α4β1 molecule (α4-integrin) expressed in the membrane of lymphocytes with vascular cell adhesion molecule (VCAM)-1 expressed on the endothelial surface which causes the capture of these lymphocytes.…”

Section: Movement Of Lymphocytes In and Out Of The Cnsmentioning

confidence: 99%

Is Central Nervous System an Immune-Privileged Site?

Shrestha

Millington

Brewer

et al. 2014

Kathmandu Univ. Med. J.

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The central nervous system (CNS) was once considered to be an immune-privileged area. However, increasing evidence shows that the central nervous system is not an immune-privileged but is an active surveillance site. There is a bi-directional communication between the central nervous system and immune system. Normally, immune cells migrate into the central nervous system microenvironment through choroid plexus and interact with the central nervous system resident cells through either through neuromediators or immunomediators. This finding has led to a significant interest in neuroimmunological interactions and investigation onto the role of the immune system in the pathology of various neurological disorders and examine whether it can be targeted to produce novel therapeutic strategies.

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Immune cell entry into the central nervous system: Involvement of adhesion molecules and chemokines

Cited by 156 publications

References 27 publications

The Blood–Brain Barrier

The Blood–Brain Barrier

1,25-Dihydroxyvitamin D₃selectively and reversibly impairs T helper-cell CNS localization

Is Central Nervous System an Immune-Privileged Site?

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Immune cell entry into the central nervous system: Involvement of adhesion molecules and chemokines

Cited by 156 publications

References 27 publications

The Blood–Brain Barrier

The Blood–Brain Barrier

1,25-Dihydroxyvitamin D3selectively and reversibly impairs T helper-cell CNS localization

Is Central Nervous System an Immune-Privileged Site?

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About

1,25-Dihydroxyvitamin D₃selectively and reversibly impairs T helper-cell CNS localization