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 |
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Additional Information: | <b>Clive S. McKimmie is joint first author of this paper.</b> |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Garside, Professor Paul and Milling, Professor Simon and Gilchrist, Dr Derek and Lee, Miss Kit and Pallas, Mr Kenny and Nibbs, Professor Rob 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 > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Blood |
Publisher: | American Society of Hematology |
ISSN: | 0006-4971 |
ISSN (Online): | 1528-0020 |
Published Online: | 06 October 2011 |
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