EFFECT OF CIRCADIAN VARIATIONS IN MUCOSAL IMMUNE RESPONSE TO FOOD ANTIGEN

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Many immune parameters oscillate rhythmically with the time ofday and the circadian clock has emerged as an important gatekeeperthat enhances fitness of the organism. In the present workwe have characterized the influence of biological rhythms on theimmune function of the intestinal mucosa and its impact on thetolerance towards oral antigens. Using multivariate statistic tests(PCA , ADL, MANOVA), we evaluated 17 parameters (cell subsets,homing receptors, activation markers and cytokines) in mesentericlymph nodes (MLN) of B6 WT mice exposed to light-dark 12:12conditions at four times (ZT5, 11, 17 and 23). PCA and ADL testsconfirmed that over a 24-hr period, three different immune configurationscan be described in MLN: at the light period (ZT 5); at thedark period (ZT17) and at the transition periods (ZT11 and 23). Thedistribution in these groups was dependent on the integrity of themolecular clock, as mice deficient in the clock gene Per2 (Per2KO),showed significant differences with WT animals (p<0.05) as well asa reduction on the oscillatory pattern. We evaluated if immune configurationsobserved at ZT5 and ZT17 could be both competent toinduce tolerance toward a fed antigen (ovalbumin-OVA). Using twomodels of tolerance, we found that the intake of the antigen duringthe late dark phase (ZT23) induced more tolerance evaluated aslower proliferation rates. Moreover, OVA specific T cells (CD4+ OTII+)with increased expression of Foxp3 transcription factor (p<0.05)and selective localization in the lamina propria was elicited by thedaily administration of OVA at the end of the dark phase. Our resultsdemonstrate that in a period of 24 h, the feeding during the