TY - JOUR
T1 - Targeting lymphatic function as a novel therapeutic intervention for rheumatoid arthritis
AU - Bouta, Echoe M.
AU - Bell, Richard D.
AU - Rahimi, Homaira
AU - Xing, Lianping
AU - Wood, Ronald W.
AU - Bingham, Clifton O.
AU - Ritchlin, Christopher T.
AU - Schwarz, Edward M.
N1 - Funding Information:
E.M.B. and R.D.B. are supported by a training grant from the NIH (T32 AR053459). H.R. is supported by an NIH grant (K08 AR067885). L.X. is supported by NIH grants (AR069789 and AR063650), a University of Rochester CTSA award (UL1 TR000042), a grant from the National Natural Science Foundation of China (grant 81220108027), and a grant from the Lymphatic Malformation Institute. R.W.W. is supported by an NIH grant (AR061307). C.T.R. is supported by NIH grants (R01 AR056702 and R01 AR069000). E.M.S. is supported by NIH grants (P30 AR069655 and R01 AR056702).
Publisher Copyright:
© 2018 Macmillan Publishers Limited, part of Springer Nature.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - Although clinical outcomes for patients with rheumatoid arthritis (RA) have greatly improved with the use of biologic and conventional DMARDs, approximately 40% of patients do not achieve primary clinical outcomes in randomized trials, and only a small proportion achieve lasting remission. Over the past decade, studies in murine models point to the critical role of the lymphatic system in the pathogenesis and therapy of inflammatory-erosive arthritis, presumably by the removal of catabolic factors, cytokines and inflammatory cells from the inflamed synovium. Murine studies demonstrate that lymphatic drainage increases at the onset of inflammatory-erosive arthritis but, as inflammation progresses to a more chronic phase, lymphatic clearance declines and both structural and cellular changes are observed in the draining lymph node. Specifically, chronic damage to the lymphatic vessel from persistent inflammation results in loss of lymphatic vessel contraction followed by lymph node collapse, reduced lymphatic drainage, and ultimately severe synovitis and joint erosion. Notably, clinical pilot studies in patients with RA report lymph node changes following treatment, and thus draining lymphatic vessels and nodes could represent a potential biomarker of arthritis activity and response to therapy. Most importantly, targeting lymphatics represents an innovative strategy for therapeutic intervention for RA.
AB - Although clinical outcomes for patients with rheumatoid arthritis (RA) have greatly improved with the use of biologic and conventional DMARDs, approximately 40% of patients do not achieve primary clinical outcomes in randomized trials, and only a small proportion achieve lasting remission. Over the past decade, studies in murine models point to the critical role of the lymphatic system in the pathogenesis and therapy of inflammatory-erosive arthritis, presumably by the removal of catabolic factors, cytokines and inflammatory cells from the inflamed synovium. Murine studies demonstrate that lymphatic drainage increases at the onset of inflammatory-erosive arthritis but, as inflammation progresses to a more chronic phase, lymphatic clearance declines and both structural and cellular changes are observed in the draining lymph node. Specifically, chronic damage to the lymphatic vessel from persistent inflammation results in loss of lymphatic vessel contraction followed by lymph node collapse, reduced lymphatic drainage, and ultimately severe synovitis and joint erosion. Notably, clinical pilot studies in patients with RA report lymph node changes following treatment, and thus draining lymphatic vessels and nodes could represent a potential biomarker of arthritis activity and response to therapy. Most importantly, targeting lymphatics represents an innovative strategy for therapeutic intervention for RA.
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U2 - 10.1038/nrrheum.2017.205
DO - 10.1038/nrrheum.2017.205
M3 - Review article
C2 - 29323343
AN - SCOPUS:85041238900
SN - 1759-4790
VL - 14
SP - 94
EP - 106
JO - Nature Reviews Rheumatology
JF - Nature Reviews Rheumatology
IS - 2
ER -