Abstract P148: Sex-dependent Colonic Immune Responses In Salt-sensitive Hypertension Meeting Abstract (Web of Science)

abstract

  • Introduction: Hypertension affects almost half of the adults in the US. Overactivation of immune system results in pathogenesis of hypertension. Given that sex differences are reported in salt-sensitive hypertension and that the gut is an important organ at the interface between gut microbiota and the host, we hypothesized that differential colonic immunity exists between male and female rats on high and low salt diets. Methods: Total RNA was isolated from the colons of male and female Dahl Salt-Sensitive (S) rats fed with either high-salt (2% NaCl) or low-salt (0.3% NaCl) diet at 9-10 weeks old (n=3/sex/diet) and subjected to transcriptome followed by pathway analyses to detect differentially enriched transcripts and biological processes (FDR<0.05). The transcripts overexpressed in the sex-matched S rats on high salt diets were defined as hypertension-associated genes. Among them, the transcripts upregulated in both sexes were inferred as sex-independent, while those upregulated exclusively in either sex were considered as sex-dependent. Results: Upregulation of colonic immunity was evident through the transcriptomic signatures of both sexes with hypertension. Among the upregulated 38 male sex-dependent transcripts, 20 were related to T cell activation including co-receptor Cd4 , co-stimulators Cd80 and Cd86 , and Th1 and Treg cells-related receptors and cytokines Tgfbr2 , Il1r1 , Il18r1 and Lif , whereas 17 out of 27 upregulated female sex-dependent transcripts were related to T cell activation including co-receptor Cd8 , co-stimulators Cd40 , Icoslg , Cd27 , and Tnfsf9 , and Th2 and Th17-related cytokines Tgfb1 , Tgfb3 , Il1b , Il23a and Gata3 . In addition, antigen presenting cells were observed with upregulated MHC II in males, whereas upregulated both MHC I and II in females with hypertension. Further, 12 out of 20 sex-independent transcripts were suggestive of B cell activation. Conclusion: Marked sex differences were noted in the levels of colonic immune function- related transcripts of S rats on high salt diet. In the colonic T cell activation related transcripts, Cd4 and MHC II were predominant in males, while Cd8 and both MHC I and II were more prevalent in females. Additionally, colonic B cell activation was relatively less dependent on sex.

authors

  • Mei, Xue
  • CHAKRABORTY, Saroj
  • Cheng, Xi
  • Yang, Tao
  • Joe, Bina

publication date

  • 2020

published in

volume

  • 76

issue

  • Suppl_1