The Peyer's Patch follicle associated epithelium (FAE) provides both an epithelial barrier over mucosal lymphoid tissue and specialized delivery of antigens to the immune system. Although the best-known function of the FAE is the transcytosis mediated by M cells, the differentiation and function of FAE must be considered as a whole. Indeed, the FAE should be viewed as a complex tissue, with several functional subsets, and direct interactions with embedded lymphocytes and underlying immune tissue. We have identified several FAE associated genes that may encode specialized receptors for transcytosis of antigens to underlying lymphoid tissue. Some of these receptors may also signal adjuvant activity for mucosal immunity. Our working hypothesis is that the FAE functions as a filter for molecules gaining access to the Peyer's Patch, and as an innate immune sensor. Consistent with this notion, expression of some genes among cells of the FAE appears to mark distinct functional subsets. We propose a study of FAE using both in vitro and in vivo models, to reveal the relationships among FAE subsets in vivo with respect to their developmental biology and function.
Three specific aims are proposed:
Specific aim 1. How are FAE phenotypic subsets related? ;
Specific aim 2. How does sub-cellular reorganization occur during differentiation of FAE and M cell phenotypes? ;
Specific aim 3. Do M cells differentiate from committed precursors or common FAE enterocytes? Information gained from the proposed studies will help the understanding of pathogenesis mechanisms of intestinal infectious diseases, and provide important targets in the design of mucosal vaccines.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Gastrointestinal Mucosal Pathobiology Study Section (GMPB)
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Rothermel, Annette L
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University of California Riverside
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Parnell, Erinn A; Walch, Erin M; Lo, David D (2017) Inducible Colonic M Cells Are Dependent on TNFR2 but Not Lt?r, Identifying Distinct Signalling Requirements for Constitutive Versus Inducible M Cells. J Crohns Colitis 11:751-760
Bennett, Kaila M; Parnell, Erinn A; Sanscartier, Candice et al. (2016) Induction of Colonic M Cells during Intestinal Inflammation. Am J Pathol 186:1166-79
Gaieb, Zied; Lo, David D; Morikis, Dimitrios (2016) Molecular Mechanism of Biased Ligand Conformational Changes in CC Chemokine Receptor 7. J Chem Inf Model 56:1808-22
Bennett, Kaila M; Gorham Jr, Ronald D; Gusti, Veronica et al. (2015) Hybrid flagellin as a T cell independent vaccine scaffold. BMC Biotechnol 15:71
Sakhon, Olivia S; Ross, Brittany; Gusti, Veronica et al. (2015) M cell-derived vesicles suggest a unique pathway for trans-epithelial antigen delivery. Tissue Barriers 3:e1004975
Bennett, Kaila M; Walker, Sharon L; Lo, David D (2014) Epithelial microvilli establish an electrostatic barrier to microbial adhesion. Infect Immun 82:2860-71
Vandrangi, P; Lo, D D; Kozaka, R et al. (2013) Electrostatic properties of confluent Caco-2 cell layer correlates to their microvilli growth and determines underlying transcellular flow. Biotechnol Bioeng 110:2742-8
Lo, David D (2013) Mucosal vaccine delivery: is M cell-targeted delivery effective in the mucosal lumen? Expert Opin Drug Deliv 10:157-61
Woodrow, Kim A; Bennett, Kaila M; Lo, David D (2012) Mucosal vaccine design and delivery. Annu Rev Biomed Eng 14:17-46
Hsieh, En-Hui; Lo, David D (2012) Jagged1 and Notch1 help edit M cell patterning in Peyer's patch follicle epithelium. Dev Comp Immunol 37:306-12

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