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Title: Halted lymphocyte egress via efferent lymph contributes to lymph node hypertrophy during hypercholesterolemia
Authors: Tay, M.H.D.
Lim, S.Y.J.
Leong, Y.F.I.
Thiam, C.H. 
Tan, K.W. 
Torta, F.T. 
Narayanaswamy, P. 
Wenk, M. 
Angeli, V. 
Keywords: Dyslipidemia
Lymph node
Lymphatic vessel
Lymphocyte egress
Mouse model
Issue Date: 2019
Publisher: Frontiers Media S.A.
Citation: Tay, M.H.D., Lim, S.Y.J., Leong, Y.F.I., Thiam, C.H., Tan, K.W., Torta, F.T., Narayanaswamy, P., Wenk, M., Angeli, V. (2019). Halted lymphocyte egress via efferent lymph contributes to lymph node hypertrophy during hypercholesterolemia. Frontiers in Immunology 10 (MAR) : 575. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Dyslipidemia is a central component of atherosclerosis and metabolic syndrome linked to chronic inflammation and immune dysfunction. Previously, we showed that hypercholesterolemic apolipoprotein E knock out (apoE?/?) mice exhibit systemic effects including skin inflammation and hypertrophic lymph nodes (LNs). However, the mechanisms accounting for LN hypertrophy in these mice remain unknown. Here, we show that hypercholesterolemia led to the accumulation of lymphocytes in LNs. We excluded that the increased number of lymphocytes in expanded LNs resulted from increased lymphocyte proliferation or entry into those LNs. Instead, we demonstrated that the egress of lymphocytes from the enlarged LN of apoE?/? mice was markedly decreased. Impairment in efferent lymphatic emigration of lymphocytes from LNs resulted from an aberrant expansion of cortical and medullary sinuses that became hyperplastic. Moreover, CCL21 was more abundant on these enlarged sinuses whereas lymph levels of sphingosine 1 phosphate (S1P) were decreased in apoE?/? mice. Normal LN size, lymphatic density and S1P levels were restored by reversing hypercholesterolemia. Thus, systemic changes in cholesterol can sequester lymphocytes in tissue draining LNs through the extensive remodeling of lymphatic sinuses and alteration of the balance between retention/egress signals leading to LN hypertrophy which subsequently may contribute to poor immunity. This study further illustrates the role of lymphatic vessels in immunity through the regulation of immune cell trafficking. Copyright © 2019 Tay, Lim, Leong, Thiam, Tan, Torta, Narayanaswamy, Wenk and Angeli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Source Title: Frontiers in Immunology
ISSN: 1664-3224
DOI: 10.3389/fimmu.2019.00575
Rights: Attribution 4.0 International
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