Gastrointestinal Immune Development and Disease

The gastrointestinal (GI) tract is one of the largest immune organs in the body. It is also host to 500 to 1000 different bacterial species and as much as 1014 bacteria. The majority of these bacteria represent commensals that play an important role in the development and maintenance of the host immune system. The careful interplay between the immune cells and the commensal bacteria allow for the host’s immune system’s ability to respond to pathogenic bacteria but to be tolerant to the commensal ones. However, how homeostasis is established and maintained in humans is very poorly understood.

Through translational studies of human tissue throughout gestation as well as from neonates and young children, the Konnikova Lab is interested in deciphering how homeostasis is established and maintained.

Dysregulation of the GI immune homeostasis leads to a number of diseases such as necrotizing enterocolitis (NEC), very early onset inflammatory bowel disease (VEO-IBD) and IBD. To facilitate with studying mucosal immunity in health and diseases, we have adapted mass cytometry (CyTOF) to perform deep immunophenotyping and functional analysis of immune cells at mucosal surfaces. Additionally, we have developed a cryopreservation method to store tissue directly with preservation of viability and functionality. These advances have allowed us to study immune dysregulation in various diseases such as NEC, VEOIBD and IBD.

CyTOF analysis of immune cells in the small intestine of a VEOIBD patient (P1) and patients with and without IBD. Kotlarz et al, Nature Genetics, 2018.

CyTOF analysis of immune cells in the small intestine of a VEOIBD patient (P1) and patients with and without IBD. Kotlarz et al, Nature Genetics, 2018.

FACS analysis of Th17 and IL17 production in an IL10 receptor deficient patient. Shouval and Konnikova et al, IBD, 2017.

FACS analysis of Th17 and IL17 production in an IL10 receptor deficient patient. Shouval and Konnikova et al, IBD, 2017.