The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the entry of peripheral tissue T lymphocytes into afferent lymphatics.

Abstract:

:Although much is known about the migration of T cells from blood to lymph nodes, less is known about the mechanisms regulating the migration of T cells from tissues into lymph nodes through afferent lymphatics. Here we investigated T cell egress from nonlymphoid tissues into afferent lymph in vivo and developed an experimental model to recapitulate this process in vitro. Agonism of sphingosine 1-phosphate receptor 1 inhibited the entry of tissue T cells into afferent lymphatics in homeostatic and inflammatory conditions and caused the arrest, mediated at least partially by interactions of the integrin LFA-1 with its ligand ICAM-1 and of the integrin VLA-4 with its ligand VCAM-1, of polarized T cells at the basal surface of lymphatic but not blood vessel endothelium. Thus, the increased sphingosine 1-phosphate present in inflamed peripheral tissues may induce T cell retention and suppress T cell egress.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Ledgerwood LG,Lal G,Zhang N,Garin A,Esses SJ,Ginhoux F,Merad M,Peche H,Lira SA,Ding Y,Yang Y,He X,Schuchman EH,Allende ML,Ochando JC,Bromberg JS

doi

10.1038/ni1534

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

42-53

issue

1

eissn

1529-2908

issn

1529-2916

pii

ni1534

journal_volume

9

pub_type

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