Gastrointestinal Mucosal Immunology Program
Intestinal epithelial cells serve as a physical barrier to microbial penetration and provide a sentinel system to warn immune cells of pathogen exposure or injury, placing them in an ideal position to regulate the balance between pro- and anti-inflammatory states. Dr. McCormick’s studies were the first to characterize a balanced system at the intestinal mucosal surface in which eukaryotic ABC transporters and their efflux products play a fundamental role in immunomodulation. This dynamic balance operates between homeostatic pathways that suppress immune responses to commensal bacteria (the P-glycoprotein/endocannabinoid axis) and inflammatory pathways that activate responses to pathogens or aberrant signals (MRP2/hepoxilin A3), and can be unhinged by a dysbiotic microbiome. Dysregulation of this critical balance contributes directly to inflammatory disorders of the intestine, as well as other mucosal surfaces.
- McCormick BA, Colgan SP, Delp-Archer C, Miller SI, Madara JL. Salmonella typhimurium attachment to human intestinal epithelial monolayers: transcellular signalling to subepithelial neutrophils. J Cell Biol. 1993 Nov;123(4):895-907.
- McCormick BA, Hofman PM, Kim J, Carnes DK, Miller SI, Madara JL. Surface attachment of Salmonella typhimurium to intestinal epithelia imprints the subepithelial matrix with gradients chemotactic for neutrophils. J Cell Biol. 1995 Dec;131(6 Pt 1):1599-608.
- Mrsny RJ, Gewirtz AT, Siccardi D, Savidge T, Hurley BP, Madara JL, McCormick BA. Identification of hepoxilin A3 in inflammatory events: a required role in neutrophil migration across intestinal epithelia. Proc Natl Acad Sci U S A. 2004 May 11;101(19):7421-6.
- Pazos M, Siccardi D, Mumy KL, Bien JD, Louie S, Shi HN, Gronert K, Mrsny RJ, McCormick BA. Multidrug resistance-associated transporter 2 regulates mucosal inflammation by facilitating the synthesis of hepoxilin A3. J Immunol. 2008 Dec 1;181(11):8044-52.
- Agbor TA, Demma Z, Mrsny RJ, Castillo A, Boll EJ, McCormick BA. The oxido-reductase enzyme glutathione peroxidase 4 (GPX4) governs Salmonella Typhimurium-induced neutrophil transepithelial migration. Cell Microbiol. 2014 Sep;16(9):1339-53.
- Zukauskas A, Mrsny RJ, Cortés Barrantes P, Turner JR, Leong JM, McCormick BA. Transporters MRP1 and MRP2 regulate opposing inflammatory signals to control transepithelial neutrophil migration during Streptococcus pneumoniae lung infection. mSphere. 2018. Jul 5;3(4).
- Szabady RL, Louissaint C, Lubben A, Xie B, Reeksting S, Tuohy C, Demma Z, Foley SE, Faherty CS, Llanos-Chea A, Olive AJ, Mrsny RJ, McCormick BA. Intestinal P-glycoprotein exports endocannabinoids to prevent inflammation and maintain homeostasis. J Clin Invest. 2018. Aug 31;128(9):4044-4056.