LTC4 MODULATES AN INFLAMMATORY RESPONSE AT THE GUT LEVEL VIA THE ACTIVATION OF CYSTEINYL LEUKOTRIENE RECEPTOR 1.

ALCAIN J; GORI S; SALAMONE G; VANZULLI S; MORA G; VERMEULEN M

Mar del Plata

Congreso; Reunión Conjunta SAIC-SAI-SAFE 2016; 2016

Leukotriene C4 (LTC4) is an important lipid mediator involved in the genesis of chronic inflammatory responses. +ts effects are mediated through the cysteinyl receptor and CysLT4/. +n previous YorMs, it has been demonstrated that LTC is able to modulate chemotaxis of dendritic cells &C and their activation state, Yith the ability to interfere Yith their maturation. Here, Ye studied the capacity of LTC to breaM the gut tolerance. For this, $AL$/c mice Yere orally inoculated Yith a single dose of 2$S Ct or LTC . z/ in zl of 2$S at the beginning of 1valbumin tolerance mg/day in drinMing Yater for days. After days, histological examination of small intestine shoYed that the intestine Yas extensively modified by the exposure to LTC, mainly evidenced through the shortening of villi, increased protrusion of goblet cells and edema in the lamina propria, together Yith a marMed recruitment of leuMocytes, mainly eosinophilicgranulocytes. Then, Ye decided to evaluate the populations recruited in mesenteric lymph node after treatment. +n the first place, LTC inhibited the CD11c CD103dendritic cells (DC), the main population associated to mucosal tolerance mean C&c CD103&C v SE/ 2$S . v ., LTC . v ., pŭ., n . Also, Ye observed a greater expression of CysLT4compared to CysLT4 mean band ratio/bactin CysLT4 vs CysLT4 . v . . v . p., n in the small intestine of mice Yhich Yas not affected by the induction of tolerance. Finally, LTC Yas able to induce the production of C& IL-17 lymphocytes in the lymph nodes of tolerated mice. +nterestingly, the use of monteluMast, an antagonist of CysLT4, Yas able to reverse the induction of Th profile mean C&IL-17 cells v SE/ 2$S, . v . LTC, v . /- . v . along Yith the recruitment of neutrophils, hoYever it had no significant effect on gut morphology. +n conclusion, LTC modulates gut homeostasis partially via CysLT4.