Editing Lymphedema (section)

==Physiology==
[[Lymph]] is formed from the fluid that filters out of blood and contains proteins, cellular debris, bacteria, etc. This fluid is collected by the initial lymph collectors that are blind-ended [[Epithelium|endothelial]]-lined vessels with fenestrated openings that allow fluids and particles as large as cells to enter. Once inside the [[lumen (anatomy)|lumen]] of the lymphatic vessels, the fluid is guided along increasingly larger vessels, first with rudimentary valves to prevent backflow, later with complete valves similar to the venous valve. Once the lymph enters the fully valved lymphatic vessels, it is pumped by a rhythmic [[Peristalsis|peristaltic]]-like action by smooth muscle cells within the lymphatic vessel walls. This peristaltic action is the primary driving force moving lymph within its vessel walls. The [[sympathetic nervous system]] regulates the frequency and power of the contractions. Lymph movement can be influenced by the pressure of nearby muscle contraction, arterial pulse pressure and the vacuum created in the chest cavity during respiration, but these passive forces contribute only a minor percentage of lymph transport. The fluids collected are pumped into continually larger vessels and through lymph nodes, which remove debris and police the fluid for dangerous microbes. The lymph ends its journey in the thoracic duct or right lymphatic duct, which drain into the blood circulation.<ref name="Visual Guide to Lymphedema" />

Several research groups have hypothesized that chronic inflammation is a key regulator in the development of lymphedema. Th cells, particularly Th2 differentiation, play a crucial role in the pathophysiology of lymphedema. Research has shown that increased expression of Th2-inducing cytokines in the epidermal cells of the lymphoedematous limb. Treatment with QBX258 has been found to decrease hyperkeratosis and fibrosis, reduce the number of CD4+ cells, and normalize the expression of Th2-inducing cytokines and IL13R by keratinocytes. These findings suggest that epidermal cells may initiate or coordinate chronic Th2 responses in lymphedema.<ref name=":1">{{Cite journal |last1=Mehrara |first1=Babak J. |last2=Park |first2=Hyeung Ju |last3=Kataru |first3=Raghu P. |last4=Bromberg |first4=Jacqueline |last5=Coriddi |first5=Michelle |last6=Baik |first6=Jung Eun |last7=Shin |first7=Jinyeon |last8=Li |first8=Claire |last9=Cavalli |first9=Michele R. |last10=Encarnacion |first10=Elizabeth M. |last11=Lee |first11=Meghan |last12=Van Zee |first12=Kimberly J. |last13=Riedel |first13=Elyn |last14=Dayan |first14=Joseph H. |date=2021-09-18 |title=Pilot Study of Anti-Th2 Immunotherapy for the Treatment of Breast Cancer-Related Upper Extremity Lymphedema |journal=Biology |volume=10 |issue=9 |pages=934 |doi=10.3390/biology10090934 |doi-access=free |issn=2079-7737 |pmc=8466465 |pmid=34571811}}</ref>

=== Role of T-Cell inflammation and Th2 response ===
Lymphedema involves a complex interplay of inflammatory processes. Recent research has shed light on the role of T-cell inflammation and the Th2 immune response in the initiation of lymphedema.<ref name=":0">{{Cite journal |last1=Avraham |first1=Tomer |last2=Zampell |first2=Jamie C. |last3=Yan |first3=Alan |last4=Elhadad |first4=Sonia |last5=Weitman |first5=Evan S. |last6=Rockson |first6=Stanley G. |last7=Bromberg |first7=Jacqueline |last8=Mehrara |first8=Babak J. |date=March 2013 |title=Th2 differentiation is necessary for soft tissue fibrosis and lymphatic dysfunction resulting from lymphedema |journal=FASEB Journal|volume=27 |issue=3 |pages=1114–1126 |doi=10.1096/fj.12-222695 |doi-access=free |issn=1530-6860 |pmc=3574290 |pmid=23193171}}</ref>

==== T-Cell inflammation and fibrosis ====
Studies have revealed that sustained lymphatic stasis results in the infiltration of CD4+ T-cells, leading to inflammation and fibrosis within affected tissues.<ref name=":0" />