D6 facilitates cellular migration and fluid flow to lymph nodes by suppressing lymphatic congestion

Lee, K. M. et al. (2011) D6 facilitates cellular migration and fluid flow to lymph nodes by suppressing lymphatic congestion. Blood, 118(23), pp. 6220-6229. (doi:10.1182/blood-2011-03-344044)

Lee, K. M. et al. (2011) D6 facilitates cellular migration and fluid flow to lymph nodes by suppressing lymphatic congestion. Blood, 118(23), pp. 6220-6229. (doi:10.1182/blood-2011-03-344044)

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Publisher's URL: http://dx.doi.org/10.1182/blood-2011-03-344044

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<sup>+</sup> APCs. Accordingly, in D6-deficient mice, inflammatory CCchemokine 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.

Item Type:Articles
Additional Information:<b>Clive S. McKimmie is joint first author of this paper.</b>
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Pallas, Mr Kenny and Nibbs, Professor Robert and Garside, Professor Paul and Milling, Professor Simon and Gilchrist, Dr Derek and Lee, Miss Kit and Cerovic, Dr Vuk and McKimmie, Dr Clive and Graham, Professor Gerard
Authors: Lee, K. M., McKimmie, C. S., Gilchrist, D. S., Pallas, K. J., Nibbs, R. J., Garside, P., McDonald, V., Jenkins, C., Ransohoff, R., Liu, L., Milling, S., Cerovic, V., and Graham, G. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Blood
Publisher:American Society of Hematology
ISSN:0006-4971
ISSN (Online):1528-0020
Published Online:06 October 2011
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
514422Regulation of the adaptive immune response by chemokine scavenging receptorsGerard GrahamMedical Research Council (MRC)G0901113Infection Immunity and Inflammation Medicine
512511The Functions of Migrating Dendritic CellsSimon MillingMedical Research Council (MRC)G0900270Infection Immunity and Inflammation Medicine