The lymphatic vasculature is a hierarchical network of vessels (capillary, pre-collector, and collector) that unidirectionally transport fluid and cells from peripheral tissue into lymph nodes (LN). Lymphatic endothelial cells (LEC) line both the lymphatic vessels in tissue as well as the lymphatic sinuses at the entry and exit point of LNs. Together, this system of vessels and sinuses plays a critical role in regulating the delivery of activated leukocytes, antigenic material, and fluid from steady-state and inflamed peripheral tissues to LNs where immune responses are initiated. Consequently, the remodeling of both peripheral and nodal lymphatic structures in various pathologies (obesity, infection, inflammation, malignancy, etc.) may significantly alter downstream immune responses either through effects on bulk transport, or alternatively, through microenvironment-dependent changes in LEC-intrinsic biology. In fact, mounting evidence indicates that LECs harbor unique, intrinsic immunological activities that couple with their continuous access to lymph-borne antigen to actively coordinate immune responses and maintain peripheral tolerance. LEC maintenance of peripheral tolerance in the LN occurs through (i) the presentation of peripheral tissue antigens by MHC class I or class II and (ii) the expression of inhibitory ligands, such as PD-L1, leading to CD8+ T cell deletion or CD4+ T cell anergy. LN LECs can also retain and exchange foreign antigens with migrating dendritic cells (DC) to promote immunological memory. However, the factors that control LEC antigen presentation versus LEC-DC antigen exchange are yet to be identified. Thus, clearly identifying how LECs handle self and foreign antigens and why this occurs will be important for understanding LEC function and how these processes influence disease. Importantly, the relative contribution of these novel LEC functionalities to immunity, in comparison to effects of bulk lymph transport, remains to be fully determined. Furthermore, how inflammatory remodeling of lymphatic vessel function and alterations of LEC phenotype contribute to local and future immune responses remain unclear.
Taken together, data collected by the field indicates that management of the lymphatic vasculature, its transport properties, and the ability to influence immunity through peripheral T cell tolerance and immunological memory, make the lymphatic vasculature and LECs key regulators of immunity. These immunological mechanisms are increasingly relevant as approaches to exploit or inhibit the lymphatic vasculature are explored for diverse applications from tumor immunotherapy, vaccine development, and chronic inflammation. The goal of this Research Topic is to establish a working model for how the lymphatic vasculature and the LECs that comprise the lymphatic vasculature contribute to immunity, tolerance and inflammation from (i) balancing immune surveillance and peripheral tolerance to (ii) initial responses to a challenge, generation of adaptive immunity, and (iii) the return to homeostasis. A deeper understanding of these processes will inform approaches for therapeutic management of the immune system.
In this Research-Topic, we welcome the submission of Original Research, Protocol, Method, Perspective, Review, and Mini Review articles that cover the following research areas:
1. The lymphatic vasculature, immune surveillance, homeostasis.
2. The lymphatic vasculature and the innate immune response.
3. Lymphatic vessels and initiation of the adaptive immune response, immune privilege, and graft immunity.
4. Leukocyte trafficking via the lymphatic vasculature.
5. Inflammation and lymphatic transport.
6. Composition of lymph and biomechanics of lymph transport – implications for immunity.
7. LEC-mediated regulation of peripheral immunological tolerance and immune evasion
8. Factors controlling self-antigen presentation by LECs and its implications for immune tolerance.
9. Lymphatic vessels, LECs, and immunological memory.
10. Immune-mediated remodeling of peripheral and nodal lymphatic networks, contraction and normalization.
11. Lymphangiogenesis, lymphatic transport, and infection.
12. Lymphatic vessel and LEC immune dysfunction in chronic conditions (obesity, hypertension, arthritis, lymphedema, etc.).
13. Tumor-associated lymphangiogenesis, anti-tumor immunity, and immunotherapy.
The lymphatic vasculature is a hierarchical network of vessels (capillary, pre-collector, and collector) that unidirectionally transport fluid and cells from peripheral tissue into lymph nodes (LN). Lymphatic endothelial cells (LEC) line both the lymphatic vessels in tissue as well as the lymphatic sinuses at the entry and exit point of LNs. Together, this system of vessels and sinuses plays a critical role in regulating the delivery of activated leukocytes, antigenic material, and fluid from steady-state and inflamed peripheral tissues to LNs where immune responses are initiated. Consequently, the remodeling of both peripheral and nodal lymphatic structures in various pathologies (obesity, infection, inflammation, malignancy, etc.) may significantly alter downstream immune responses either through effects on bulk transport, or alternatively, through microenvironment-dependent changes in LEC-intrinsic biology. In fact, mounting evidence indicates that LECs harbor unique, intrinsic immunological activities that couple with their continuous access to lymph-borne antigen to actively coordinate immune responses and maintain peripheral tolerance. LEC maintenance of peripheral tolerance in the LN occurs through (i) the presentation of peripheral tissue antigens by MHC class I or class II and (ii) the expression of inhibitory ligands, such as PD-L1, leading to CD8+ T cell deletion or CD4+ T cell anergy. LN LECs can also retain and exchange foreign antigens with migrating dendritic cells (DC) to promote immunological memory. However, the factors that control LEC antigen presentation versus LEC-DC antigen exchange are yet to be identified. Thus, clearly identifying how LECs handle self and foreign antigens and why this occurs will be important for understanding LEC function and how these processes influence disease. Importantly, the relative contribution of these novel LEC functionalities to immunity, in comparison to effects of bulk lymph transport, remains to be fully determined. Furthermore, how inflammatory remodeling of lymphatic vessel function and alterations of LEC phenotype contribute to local and future immune responses remain unclear.
Taken together, data collected by the field indicates that management of the lymphatic vasculature, its transport properties, and the ability to influence immunity through peripheral T cell tolerance and immunological memory, make the lymphatic vasculature and LECs key regulators of immunity. These immunological mechanisms are increasingly relevant as approaches to exploit or inhibit the lymphatic vasculature are explored for diverse applications from tumor immunotherapy, vaccine development, and chronic inflammation. The goal of this Research Topic is to establish a working model for how the lymphatic vasculature and the LECs that comprise the lymphatic vasculature contribute to immunity, tolerance and inflammation from (i) balancing immune surveillance and peripheral tolerance to (ii) initial responses to a challenge, generation of adaptive immunity, and (iii) the return to homeostasis. A deeper understanding of these processes will inform approaches for therapeutic management of the immune system.
In this Research-Topic, we welcome the submission of Original Research, Protocol, Method, Perspective, Review, and Mini Review articles that cover the following research areas:
1. The lymphatic vasculature, immune surveillance, homeostasis.
2. The lymphatic vasculature and the innate immune response.
3. Lymphatic vessels and initiation of the adaptive immune response, immune privilege, and graft immunity.
4. Leukocyte trafficking via the lymphatic vasculature.
5. Inflammation and lymphatic transport.
6. Composition of lymph and biomechanics of lymph transport – implications for immunity.
7. LEC-mediated regulation of peripheral immunological tolerance and immune evasion
8. Factors controlling self-antigen presentation by LECs and its implications for immune tolerance.
9. Lymphatic vessels, LECs, and immunological memory.
10. Immune-mediated remodeling of peripheral and nodal lymphatic networks, contraction and normalization.
11. Lymphangiogenesis, lymphatic transport, and infection.
12. Lymphatic vessel and LEC immune dysfunction in chronic conditions (obesity, hypertension, arthritis, lymphedema, etc.).
13. Tumor-associated lymphangiogenesis, anti-tumor immunity, and immunotherapy.
