Daniel Zegarra Ruiz

Project Summary:

Autoimmune diseases are a major health problem affecting over 200 million people worldwide and represent one of the leading causes of death for women under 65 years old. However, current treatments for autoimmunity are merely aimed at suppressing the immune system without treating the cause, which leads to serious adverse effects. Therefore, finding safer approaches is key to effectively control these chronic disorders.

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting over 250,000 patients in the U.S. that leads to constant inflammation in, and damage to, various organs due to an aberrant immune attack against our own tissues.Changes in the bacterial communities that colonize our gut have been linked to autoimmune diseases. Interestingly, diet has been demonstrated to shape the composition of the gut microbes and thus, affect immune responses.

Resistant starch (RS) is a dietary component that is used as an energy source by the gut microbes that in turn produce substances that dampen overactive immune responses. Therefore, I seek to better understand the effects of RS on immune cells in a model of SLE.

We have found that RS increases the lifespan of SLE-prone mice, and changes the immune populations and gut microbes residing in the gut. Given that a substance that the immune system uses to communicate with each other, a cytokine (specifically, an interferon), is critical for causing inflammation in SLE patients,I hypothesize that RS will protect from serious autoimmune manifestations by controlling this cytokine.

I will study if decreasing the number of certain immune cells responsible for producing this cytokine, the so called plasmacytoid dendritic cells, is linked to decreased levels of this communication pathway between immune and tissue cells. I expect that RS will modulate the traffic and function of these interferon-producing immune cells, and thereby will suppress manifestations of the disease from SLE-related inflammation.

Zegarra-Ruiz’s project was published in Cell Host & Microbe early 2019 (https://doi.org/10.1016/j.chom.2018.11.009)