https://www.cell.com/trends/immunology/pdf/S1471-4906(15)00198-2.pdf

Revisiting the Mechanisms of CNS Immune Privilege.

The mammalian circulatory system comprises both the cardiovascular system and the lymphatic system. In contrast to the blood vascular circulation, the lymphatic system forms a unidirectional transit pathway from the extracellular space to the venous system. It actively regulates tissue fluid homeostasis, absorption of gastrointestinal lipids, and trafficking of antigen-presenting cells and lymphocytes to lymphoid organs and on to the systemic circulation. The cardinal manifestation of lymphatic malfunction is lymphedema. Recent research has implicated the lymphatic system in the pathogenesis of cardiovascular diseases including obesity and metabolic disease, dyslipidemia, inflammation, atherosclerosis, hypertension, and myocardial infarction. Here, we review the most recent advances in the field of lymphatic vascular biology, with a focus on cardiovascular disease.

Lymphatic System in Cardiovascular Medicine

Recent discoveries of novel functions and diverse origins of lymphatic vessels have drastically changed our view of lymphatic vasculature. Traditionally regarded as passive conduits for fluid and immune cells, lymphatic vessels now emerge as active, tissue-specific players in major physiological and pathophysiological processes. Lymphatic vessels show remarkable plasticity and heterogeneity, reflecting their functional specialization to control the tissue microenvironment. Moreover, alternative developmental origins of lymphatic endothelial cells in some organs may contribute to the diversity of their functions in adult tissues. This review aims to summarize the most recent findings of organotypic differentiation of lymphatic endothelial cells in terms of their distinct (patho)physiological functions in skin, lymph nodes, small intestine, brain, and eye. We discuss recent advances in our understanding of the heterogeneity of lymphatic vessels with respect to the organ-specific functional and molecular specialization of lymphatic endothelium, such as the hybrid blood-lymphatic identity of Schlemm's canal, functions of intestinal lymphatics in dietary fat uptake, and discovery of meningeal lymphatic vasculature and perivascular brain lymphatic endothelial cells.

/pdf/organ-specific-lymphatic-vasculature-from-development-to-58ukjtxhmd.pdf

Organ-specific lymphatic vasculature: From development to pathophysiology

T cells are required for immune surveillance of the central nervous system (CNS); however, they can also induce severe immunopathology in the context of both viral infections and autoimmunity. The mechanisms that are involved in the priming and recruitment of T cells to the CNS are only partially understood, but there has been renewed interest in this topic since the 'rediscovery' of lymphatic drainage from the CNS. Moreover, tissue-resident memory T cells have been detected in the CNS and are increasingly recognized as an autonomous line of host defence. In this Review, we highlight the main mechanisms that are involved in the priming and CNS recruitment of CD4+ T cells, CD8+ T cells and regulatory T cells. We also consider the plasticity of T cell responses in the CNS, with a focus on viral infection and autoimmunity.

T cell responses in the central nervous system

The general functions of lymphatic vessels in fluid transport and immunosurveillance are well recognized. However, accumulating evidence indicates that lymphatic vessels play active and versatile roles in a tissue- and organ-specific manner during homeostasis and in multiple disease processes. This Review discusses recent advances to understand previously unidentified functions of adult mammalian lymphatic vessels, including immunosurveillance and immunomodulation upon pathogen invasion, transport of dietary fat, drainage of cerebrospinal fluid and aqueous humor, possible contributions toward neurodegenerative and neuroinflammatory diseases, and response to anticancer therapies.

Biological functions of lymphatic vessels

Lymphatic endothelial cells (LECs) directly express peripheral tissue antigens and induce CD8 T-cell deletional tolerance. LECs express MHC-II molecules, suggesting they might also tolerize CD4 T c ...

/pdf/roles-of-lymphatic-endothelial-cells-expressing-peripheral-53zsv56tzd.pdf

Priscila Riccardi

Papers

Roles of lymphatic endothelial cells expressing peripheral tissue antigens in CD4 T-cell tolerance induction