Cell types and molecules commonly associated with autoimmune diseases appear to be normal components of intestinal immunity

Researchers from Peter Gorer’s Department of Immunobiology have determined that features of the immune system previously considered hallmarks of autoimmune diseases are normal components of the immune system in the human gut that interact with each other alongside bacteria. The study is published in Nature.

The authors used a combination of spatial transcriptomics and multiplexed single-cell technologies to localize a B cell subtype in normal intestinal lymphoid tissue that is also known to be enriched in the blood in patients with the autoimmune disease lupus.

When in the intestines, these “DN2” B cells interact with dendritic cells that co-express the lupus autoantigens DNASE1L3 and C1q, adjacent to bacteria.

The normal functions of DN2 B cells, DNASE1L3, and C1q in the intestines are likely related to bacterial recognition, bacterial killing, and removal of bacterial waste, including DNA. Failure of such a system could result in the persistence of bacterial DNA that could stimulate an autoimmune response.

The link between gut bacteria and autoimmunity has been challenging to understand. The authors hope that identifying how the immune system normally deals with bacteria in the gut could be the key to preventing certain autoimmune diseases.

“Our data comes largely from untargeted computational analyzes of human tissues that have the ability to generate unexpected findings. The unexpected outcomes helped us understand how the gut immune system interacts with the extensive gut microbiota. We propose that the body could be exposed to DNA from bacteria, a key autoantigen in the autoimmune disease lupus, when these components of the gut immune system fail,” says Professor Jo Spencer.