Inflammatory bowel diseases
Crohn's disease (CD) and Ulcerative Colitis (UC) that constitute IBD are caused by imbalance between Th1 and Th17 immune cells, and Foxp3+ T-regulatory immune cells. However, in response to environmental and gut microbial triggers, T cell immune balance is disrupted which lead to inflammation in IBD.
It is shown that salt (sodium) can alter the balance between pathogenic Th17 and Treg cells. We identified that extracellular potassium induces the generation of Foxp3+ Tregs in human by enhancing TGF-β1-signaling. We found that extracellular potassium activates Smad 2 and 3 while suppresses Smad7 and SGK1 in human T cells. We found that extracellular potassium not only induces Foxp3 expression in human T cells but also inhibited generation of human Th1 and Th17 cells.
We translated these findings in a prospective cohort of nearly 170,000 US women who had been followed up for over 20 years. Among a total of 194,711 women over a follow-up of 3,220,247 person-years, we documented 273 cases of CD and 335 cases of UC. Dietary intake of potassium (Ptrend = 0.005) but not sodium (Ptrend = 0.44) was inversely associated with risk of CD. Although, both dietary potassium and sodium were not significantly associated with risk of UC, there was a suggestion of an inverse association with dietary potassium (Ptrend = 0.08). The association of potassium with risk of CD and UC appeared to be modified by loci involved in the TH17 pathway that have previously been associated with susceptibility to CD, particularly SNP rs7657746 (IL21). Dietary potassium is inversely associated with risk of CD potentially by regulating immune tolerance through its effect on Tregs and Th17 pathway.
Translational Health Science & Technology Institute
Massachusetts General Hospital and Harvard Medical School