Understanding and Overcoming Impaired Interstitial Fluid Uptake and Lymph Transport in Disease

The lymphatic vasculature is an essential component in the regulation of tissue fluid and macromolecule homeostasis, immune surveillance, dietary fat absorption and lipoprotein recycling, and clearance and/or transport of tissue macromolecules and signaling particles. Within each of these physiological roles, the biophysical properties and cellular components of the lymphatic vasculature are highly specialized to the specific draining organ and function. Lymphatic endothelial cells and lymphatic mural cells rapidly integrate physical and biochemical stimuli to actively modify their function to regulate lymph uptake and lymph transport. While lymphedema is the classic manifestation of catastrophic lymphatic failure, lymphatic dysfunction, and the ensuing lymphatic insufficiency, is now widely appreciated as a contributor to the pathophysiology of various inflammatory and cardiometabolic diseases, and congenital disorders. Despite this, there remains a dearth of pharmacological tools or delivery platforms available to patients to specifically target the lymphatic vasculature and methods to properly validate their impact.

The mission of this Research Topic is to highlight novel advances in our understanding of the structural or signaling mechanisms that regulate fluid and macromolecule uptake at the lymphatic capillary, the ionic and transcriptional regulation of lymphatic muscle cells, lymph transport at the system level, and lymph targeted drug-design and delivery platforms within the context of congenital or acquired disease states.

We welcome submission of original research articles on, but not limited to, the following topics:

• Initial Lymphatic Morphogenesis in Congenital Disorders
• Lymphatic Endothelial Primary Valves and Cell-Cell Junction Regulation
• Lymphatic Valvulogeneis and Assessment of Valve Structure-Function Relationship
• Lymphatic Mural Cell Identity and Recruitment
• Lymphatic Muscle Ionic or Contractile Dysfunction in Disease
• Methodologies of Lymph Flow Assessment from Various Organs
• Lymph Targeting Therapies or Delivery Systems
• Lymphatic Dysfunction in Disease

Please contact the organizers of this Research Topic regarding the suitability of a potential review article.

Dr. Natalie Trevaskis hereby declares the following potential competing interests:
I am an inventor of a lymph-directing glyceride prodrug technology that has been patented and licensed via a commercial agreement with Seaport Therapeutics.
I am currently receiving funding from Moderna and Protagonist Therapeutics.
I have consulted or engaged with the following companies in the past 5 years: Amgen (USA), BioNTech (Europe), Eli Lily (USA), Genentech (USA), Janssen (USA), Merck (USA), Moderna (USA/Australia), Noxopharm (Australia), Pfizer (USA) and Protagonist (USA)

Keywords: Lymphatic Malformation, Lymph Uptake, Lymph Transport, Lymphatic Contraction, Lymphatic Insufficiency, Lymphatic Dysfunction, Lymph-Directed Therapy

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.