The role of core TNF/LIGHT family members in lymph node homeostasis and remodeling.
Lymph nodes (LNs) maintain active homeostasis at steady state. However, in response to changes in the local environment, such as local infection, cancer, vaccination, and autoimmune disease, dramatic remodeling of LN occurs. This remodeling includes changes in size, lymph and blood flow, immune cell trafficking and cellularity, lymphatic and blood vessel growth and activation, as well as microarchitecture. Therefore, inflammatory conditions often lead to enlarged nodes; after local inflammation resolves, LNs actively regress in size and return to steady state. Remodeling of lymphatic vessels (LVs) and blood vessels (BVs) during both the expansion and regression phases are key steps in controlling LN size as well as function. The cells, membrane-associated molecules, and soluble cytokines that are essential for LV and BV homeostasis as well as dynamic changes in the expansion and regression phases have not been well defined. Understanding the underlying cellular and molecular mechanisms behind LN remodeling would help us to better control undesired immune responses (e.g. inflammation and autoimmune diseases) or promote desired responses (e.g. antitumor immunity and vaccination). In this review, we focus on how the closely related tumor necrosis factor (TNF) members: LIGHT (TNFSF14), lymphotoxin-αβ, and TNF-α contribute to the remodeling of LNs at various stages of inflammation.
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Mingzhao
M
Zhu
Yang-Xin
YX
Fu
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement; D060833:Cellular Microenvironment / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D008198:Lymph Nodes / Q000098:blood supply / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D042601:Lymphatic Vessels / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D053361:Lymphotoxin alpha1, beta2 Heterotrimer / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology*; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D053361:Lymphotoxin alpha1, beta2 Heterotrimer; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha