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Pathophysiology of lymphatic drainage of the central nervous system: implications for the pathophysiology of multiple sclerosis

Pathophysiology of lymphatic drainage of the central nervous system: implications for the pathophysiology of multiple sclerosis
Pathophysiology of lymphatic drainage of the central nervous system: implications for the pathophysiology of multiple sclerosis
Autoimmune inflammation in the central nervous system (CNS) plays a significant role in multiple sclerosis (MS), suggesting that regional lymph nodes are involved in pathogenesis of the disease. The brain has two fluids that drain to lymph nodes: cerebrospinal fluid (CSF) and interstitial fluid (ISF). CSF drains via nasal lymphatics and carries antigens, antigen-presenting cells (APCs), and inflammatory cells to cervical lymph nodes (CLNs). There are no conventional lymphatics in the parenchyma of the CNS; instead, ISF and soluble antigens drain to lymph nodes along narrow basement membranes in the walls of capillaries and arteries. This route is too narrow to allow the migration of APCs. Lymphatic drainage of CSF and ISF appears to confer tolerance to CNS proteins upon the CLNs. Such tolerance may be eclipsed when systemic exposure to brain antigens primes lymphocytes against CNS antigens, as occurs in experimental autoimmune encephalomyelitis. Similar mechanisms may apply to the pathogenesis of MS
978-0-12-800763-1
479-501
Elsevier
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Carare, Roxanna O.
0478c197-b0c1-4206-acae-54e88c8f21fa
Hawkes, Cheryl A.
a5bad078-e0fe-462c-989e-f0acd95892de
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Minagar, Alireza
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Carare, Roxanna O.
0478c197-b0c1-4206-acae-54e88c8f21fa
Hawkes, Cheryl A.
a5bad078-e0fe-462c-989e-f0acd95892de
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Minagar, Alireza

Weller, Roy O., Carare, Roxanna O., Hawkes, Cheryl A. and Galea, Ian (2015) Pathophysiology of lymphatic drainage of the central nervous system: implications for the pathophysiology of multiple sclerosis. In, Minagar, Alireza (ed.) Multiple Sclerosis: A Mechanistic View. Elsevier, pp. 479-501. (doi:10.1016/B978-0-12-800763-1.00019-1).

Record type: Book Section

Abstract

Autoimmune inflammation in the central nervous system (CNS) plays a significant role in multiple sclerosis (MS), suggesting that regional lymph nodes are involved in pathogenesis of the disease. The brain has two fluids that drain to lymph nodes: cerebrospinal fluid (CSF) and interstitial fluid (ISF). CSF drains via nasal lymphatics and carries antigens, antigen-presenting cells (APCs), and inflammatory cells to cervical lymph nodes (CLNs). There are no conventional lymphatics in the parenchyma of the CNS; instead, ISF and soluble antigens drain to lymph nodes along narrow basement membranes in the walls of capillaries and arteries. This route is too narrow to allow the migration of APCs. Lymphatic drainage of CSF and ISF appears to confer tolerance to CNS proteins upon the CLNs. Such tolerance may be eclipsed when systemic exposure to brain antigens primes lymphocytes against CNS antigens, as occurs in experimental autoimmune encephalomyelitis. Similar mechanisms may apply to the pathogenesis of MS

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Published date: 11 November 2015
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 384478
URI: https://eprints.soton.ac.uk/id/eprint/384478
ISBN: 978-0-12-800763-1
PURE UUID: 48ff46b6-67d0-4e0e-8ce0-c777229ae115
ORCID for Ian Galea: ORCID iD orcid.org/0000-0002-1268-5102

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Date deposited: 30 Nov 2015 09:47
Last modified: 06 Jun 2018 12:46

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