Paneth Cells in Intestinal Homeostasis and Inflammation

Antimicrobial proteins (AMPs) play a central role in enabling epithelial surfaces to regulate the intestinal microbiota. These AMPs represent an evolutionary ancient innate immune host defense mechanism that shapes the composition of the normal intestinal microbial community and restricts colonization by potential pathogens. Highly specialized Paneth cells located at the base of the intestinal crypts of and produce alfa-defensins, lysozyme and RNase.  Mice deficient in Paneth cell antimicrobials are highly susceptible to Salmonella infection. Paneth cell alpha-defensins also mediate regulation of segmented filamentous bacteria (SFBs) and the frequencies of Th17 cells. Thus, Paneth cells AMPs play an indispensable role in regulation of microbiota-host interactions under steady state and inflammatory conditions.  Our experiments revealed that IFN-gamma production by CD4+ Th1 cells during mucosal responses to the protozoan parasite Toxoplasma gondii triggers Paneth cell death. We are interested in identifying mechanisms of Paneth cell death and the effects on Paneth cell loss on the intestinal inflammation.