Abstract P189.2: Aberrant Trafficking Of Intestinal Immune Cells In Salt-sensitive Hypertension

Abstract

Hypertension is characterized by an inflammatory response, which precedes the clinical detection of organ damage. Yet, the activation and origin of target organ infiltrating immune cells are not fully understood. This study takes a systems view on inflammation in experimental hypertension and aims to investigate the extent to which the gut-associated immune cells contribute to the immune response in salt-sensitive hypertension. Immune cell trafficking from the intestine to hypertensive target organs was analyzed using in vivo labelling of intestinal immune cells via targeted UV-photoconversion in Kaede -transgenic mice. Salt-sensitive hypertension was induced in 8-10 week old male mice by oral N-nitro-L-arginine methylester (L-NAME) pretreatment (0.5 mg/ml) and two 3-week high-salt feedings (HSD, 4% NaCl-diet, 1% drinking water), separated by a 2-week normal-salt (NSD, 0.5% NaCl-diet) interval. Hypertensive organ damage and photolabelled immune cells (5d post photoconversion) were analyzed. HSD-fed mice displayed target organ damage as indicated by upregulation of mRNA-expression of markers of kidney damage ( Ngal ), inflammation ( Ccl2 ) and fibrosis ( Col3a1 ) (2^-ddCT Sham vs HTN: 1.5±1.3 vs 5.5±3.1, 1.2±0.8 vs 2.7±1.4, 1.0±0.3 vs 2.2±0.7, respectively). Intestinal immune cell trafficking was observed both in homeostasis (NSD) and disease (HSD). Infiltration of photolabelled Kaede red ( Kred+ ) intestinal immune cells was detected in various organs, namely the mesenteric lymph nodes, spleen, blood and bone marrow, as well as target organs of hypertension, namely the kidney, heart and eye. In the kidney, B-cells (39.9 ± 24.2% (NSD), 66.8 ± 5.8% (HSD) of CD45+ Kred+ cells) and T-cells (32.5 ± 18.3% (NSD), 10.1 ± 4.4% (HSD) of CD45+ Kred+ cells) were among the major migrating populations. Salt-sensitive hypertension was characterized by a dysregulation of the intestinal-renal immune cell axis. Immune cells originating from the intestine migrate and populate various organs, both in physiological homeostasis and in an aberrant manner in salt-sensitive hypertension. Our findings provide insight into mechanisms underlying hypertension-induced organ damage and could argue for interventions targeting intestinal immune cells.