P060 - INFLAMMATION-ASSOCIATED COLONIC LYMPHATIC ARCHITECTURE DISRUPTION IS AMELIORATED BY IRISIN A CHRONIC RODENT MODEL OF IBD
(Room Poster Hall)
19 Jan 18
5:30 PM
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7:00 PM
Tracks:
Clinical and Research Challenges
Background: The lymphatics are the main transport of lymph (containing fluid, macromolecules, and immunological components such as cells and cytokines) from the parenchymal tissues to the lymph nodes. Inflammation-induced lymphangiogenesis and lymphatic dysfunction occurs in pathologies such as IBD. However, it is not fully understood what drives the lymphatic hyperproliferation and dysfunction, or how local tissue cytokines (known to be significantly altered in IBD patients) associate with IBD GI lymphatic changes. Furthermore, IBD treatments have poor patient outcomes. Here we test the effect of exogenous treatment with irisin, an adipomyokine released during exercise, on immunological factors to determine if it could exert an anti-inflammatory effect during chronic gut inflammation. Methods: 2-month old, male, Sprague Dawley rats instilled rectally with TNBS/Vehicle solutions for 4-weeks. 1-week after TNBS initiation, irisin-treated rats were given bi-weekly irisin injections. Guts were scored for histopathology and assessed by immunofluorescence of lymphatic and immunological changes. Results: TNBS rats demonstrated hyperproliferation of lymphatic vessels in the colonic mucosa/submucosa compartments. Irisin-treated TNBS rats showed resolution of this phenotype. Furthermore, there was an associated elevation of TNF-⍺ in colonic sites with elevated lymphatic investment; no increases in IL-4, IL-10, or IFN-𝜸 were observed. Irisin-treated TNBS rats also had significantly decreased TNF-⍺ in the gut. Conclusions: These findings indicate the lymphatic phenotype in a chronic, TNBS model fits what is observed in IBD patients. The immunological driver supports a TNF-⍺-mediated mechanism. Furthermore, we have tested for the first time a novel biological, irisin, that shows indications of treating TNBS-induced IBD by simultaneously ameliorating the lymphatic hyperproliferation in the colonic compartments and reducing the TNF-⍺-mediated inflammation.