Skip to Main Content

Welcome to the Kriegel Lab

The Microbiota in Immune-Mediated Diseases

Research Overview

Cladogram generated from IgA-Seq data of patients with antiphospholipid syndrome and control subjects.

The gut microbiota, the collection of trillions of commensals colonizing the gastrointestinal tract, does not elicit a pathologic immune response in healthy hosts even though immune cells are constantly in contact with microbial antigens at the mucosal surfaces. This phenomenon is partly due to the fact that the human microbiota and immune system have co-evolved for millennia with the host. Diet and environmental influences that have shaped these processes in the past are very different in today's societies. Recent changes in the gut microbial community composition are thought to contribute to metabolic and immune-mediated diseases.

An emerging theme in autoimmunity research is that outgrowth of detrimental commensals ("pathobionts") or loss of beneficial commensals ("symbionts") unleashes the autoimmune process in a genetically susceptible host by various mechanisms. While evidence exists for this paradigm in some mouse models, the proof in human autoimmune diseases is still outstanding.

Major aims of this laboratory are to define the microbial community composition of gastrointestinal, cutaneous and oral microbiomes in autoimmune diseases, to study host-microbiota interactions in vitro and vivo, and to potentially prove causal relationships using humanized gnotobiotic animals. The ultimate goal is to develop novel biomarkers and therapeutic strategies for human autoimmune diseases.

The study “Translocation of a gut pathobiont drives autoimmunity in mice and humans” by Manfredo Vieira et al. published on March 9, 2018, in Science can be accessed without a paywall via our website using the following links:

A 3-minute video summarizing this work can be found published here on YouTube.

Click here to read the accompanying YaleNews article.

ONLINE COVER Lupus: No Longer a Lone Wolf. Lupus (represented by the wolf, Canis lupus) is a chronic autoimmune disorder that progresses over decades. Greiling et al. analyzed commensal bacteria in lupus patients and identified species with Ro60 proteins similar to human Ro60, an early autoantigen in lupus. Bacterial Ro60 could activate patient lymphocytes, and colonization of mice with the bacterium instigated lupus-like symptoms. These results suggest that immune recognition of a bacterial protein leads to cross-reactive immune cells targeting the human version, thereby initiating lupus. [CREDIT: MJURIK/SHUTTERSTOCK]

Our study in collaboration with the Wolin laboratory entitled “Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus” by Greiling et al. published on March 28, 2018, in Science Translational Medicineis accessible by clicking here to visit the Science Magzine website.

A 2-minute video summarizing this work can be found published here on YouTube.

Click here to read the accompanying YaleNews article.