Summary: A new study reports salt could be a possible trigger for inflammation in multiple sclerosis. Researchers report cells in a high salt environment show activation of the beta catenin/Wnt signaling pathway, a pathway previously implicated in disrupting regulatory T cells and triggering inflammation.
Researchers at Yale have identified a high-salt environment as one of the contributing factors to the development of multiple sclerosis (MS).
In a new study published Oct. 29 in the journal Nature Immunology, they report just how salt can trigger the potentially disabling autoimmune disorder.
First author Tomokazu Sumida, a researcher in the lab of David Hafler, the William S. and Lois Stiles Edgerly Professor of Neurology and professor of immunobiology, and colleagues report that cells in a high-salt environment show activation of the beta-catenin/Wnt signaling pathway. This pathway, which also been implicated in the development of cancer tumors, disrupts regulatory T cells and triggers inflammation.
The risk of developing MS is thought to increase by interaction between relatively common genetic variants and environmental factors. In addition to salt, vitamin D deficiency, smoking, and obesity have been linked to development of MS, researchers say.
Source: Bill Hathaway – Yale
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Original Research: Abstract for “Activated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity” by Tomokazu Sumida, Matthew R. Lincoln, Chinonso M. Ukeje, Donald M. Rodriguez, Hiroshi Akazawa, Tetsuo Noda, Atsuhiko T. Naito, Issei Komuro, Margarita Dominguez-Villar & David A. Hafler in Nature Immunology. Published October 29 2018.
Activated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity
The ability to mentalize, or theory of mind (ToM), is sexually Foxp3+ regulatory T cells (Treg cells) are the central component of peripheral immune tolerance. Whereas a dysregulated Treg cytokine signature has been observed in autoimmune diseases, the regulatory mechanisms underlying pro- and anti-inflammatory cytokine production are elusive. Here, we identify an imbalance between the cytokines IFN-γ and IL-10 as a shared Treg signature present in patients with multiple sclerosis and under high-salt conditions. RNA-sequencing analysis on human Treg subpopulations revealed β-catenin as a key regulator of IFN-γ and IL-10 expression. The activated β-catenin signature was enriched in human IFN-γ+ Treg cells, as confirmed in vivo with Treg-specific β-catenin-stabilized mice exhibiting lethal autoimmunity with a dysfunctional Treg phenotype. Moreover, we identified prostaglandin E receptor 2 (PTGER2) as a regulator of IFN-γ and IL-10 production under a high-salt environment, with skewed activation of the β-catenin–SGK1–Foxo axis. Our findings reveal a novel PTGER2–β-catenin loop in Treg cells linking environmental high-salt conditions to autoimmunity.