Circadian clock control of gut homing receptor expression

Los Cocos Cordoba

Otro; Advanced Course on Mucosal Immunology-Society for Mucosal Immunology; 2018

In the intestine, the circadian clock orchestrates the temporal organization of many aspects of physiology including immunity. As gut homing receptors (gHR) direct cells towards effector sites, variations in the intestinal environment over a circadian period could modulate the trafficking phenotype of immune cells. We analyzed gHR expression over 24h in MLN lymphocyte subpopulations in C57BL/6 mice housed in 12:12 light-dark conditions at different times (ZT5, 11, 17 and 23) using flow cytometry. In B cells, increments of the α4β7 integrin and CCR9 were observed at ZT17 and ZT11, respectively (p<0.05). In T cell subsets instead, reduced absolute numbers of α4β7+, CCR9+ and α4β7+CCR9+ were found at ZT11 in both CD4 and CD8 lymphocytes (p<0.05). Expression of gHR relies on the interaction with dendritic cells (DCs); therefore, we evaluated subpopulations of DCs present in MLN afferent lymphatics at different ZT. CD11c+MHCII+ DCs were more abundant during the dark period (p<0.05) while CD11c+MHCII+CD11blow DCs predominated along 24h (p<0.05). DCs isolated at ZT11 and ZT17 from WT donors showed higher ability to induce the expression of gHR on CD4 T cells after 48h of co-culture. This capacity seems to require the integrity of molecular clock as Per2KO mice exhibited an opposite pattern, with higher gHR induction at ZT 5 and 23. Our results demonstrate that the circadian clock participates in the synchronization of gHR expression. This event depends on DCs function and allows the appropriate recirculation to lamina propria in order to maintain intestinal homeostasis.