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D6 facilitates cellular migration and fluid flow to lymph nodes by suppressing lymphatic congestion.
- Source :
-
Blood [Blood] 2011 Dec 01; Vol. 118 (23), pp. 6220-9. Date of Electronic Publication: 2011 Oct 06. - Publication Year :
- 2011
-
Abstract
- Lymphatic endothelial cells are important for efficient flow of antigen-bearing fluid and antigen-presenting cells (APCs) from peripheral sites to lymph nodes (LNs). APC movement to LNs is dependent on the constitutive chemokine receptor CCR7, although how conflicting inflammatory and constitutive chemokine cues are integrated at lymphatic surfaces during this process is not understood. Here we reveal a previously unrecognized aspect of the regulation of this process. The D6 chemokine-scavenging receptor, which is expressed on lymphatic endothelial cells (LECs), maintains lymphatic surfaces free of inflammatory CC-chemokines and minimizes interaction of inflammatory leukocytes with these surfaces. D6 does not alter the level of CCR7 ligands on LECs, thus ensuring selective presentation of homeostatic chemokines for interaction with CCR7(+) APCs. Accordingly, in D6-deficient mice, inflammatory CC-chemokine adherence to LECs results in inappropriate perilymphatic accumulation of inflammatory leukocytes at peripheral inflamed sites and draining LNs. This results in lymphatic congestion and impaired movement of APCs, and fluid, from inflamed sites to LNs. We propose that D6, by suppressing inflammatory chemokine binding to lymphatic surfaces, and thereby preventing inappropriate inflammatory leukocyte adherence, is a key regulator of lymphatic function and a novel, and indispensable, contributor to the integration of innate and adaptive immune responses.
- Subjects :
- Adaptive Immunity immunology
Animals
Antigen-Presenting Cells cytology
Antigen-Presenting Cells immunology
Chemokine CCL2 immunology
Chemokine CCL2 metabolism
Chemokine CCL5 immunology
Chemokine CCL5 metabolism
Endothelial Cells cytology
Endothelial Cells metabolism
Immunity, Innate immunology
Leukocytes cytology
Leukocytes immunology
Lymph immunology
Lymph metabolism
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Receptors, CCR2 immunology
Receptors, CCR2 metabolism
Receptors, CCR7 immunology
Receptors, CCR7 metabolism
Receptors, Chemokine genetics
Body Fluids immunology
Cell Movement immunology
Endothelial Cells immunology
Lymph Nodes immunology
Receptors, Chemokine immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 118
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 21979941
- Full Text :
- https://doi.org/10.1182/blood-2011-03-344044