W. Allan Walker

Department of Pediatrics
Mucosal Immunology Laboratory
Massachusetts General Hospital - East
114 16th Street (114-3503)
Charlestown, MA 02129-4404
Tel: 617-726-7988
Fax: 617-726-4172
email:wwalker@partners.org
10 post doctoral fellows, 2 graduate students

The overall mission of this laboratory is to study antigen uptake from the intestinal lumen and its presentation to mucosal lymphocytes under physiologic and pathologic conditions. It has recently been noted that the intestinal epithelium expresses MHC class II antigen and may be able to present foreign antigens to T cells in the mucosa. Before weaning in the rodent, this MHC class II antigen is not expressed on normal intestinal epithelium but may be induced under inflammatory conditions. We have been examining the role of breast milk in controlling the expression of this surface molecule. These studies involve examination of MHC class II with immunohistochemical and molecular biologic techniques.

The polymeric immunoglobulins, IgA and IgM, form the first line of defense against infection of mucosal tissues. These antibodies, which are produced by subepithelial plasma cells, are actively transported in a receptor-mediated process across the mucosal epithelium and released into secretions. Research in this laboratory focuses on the molecular and cellular mechanisms by which the polymeric immunoglobulin receptor (pIgR) mediates this transport. We are utilizing a model system in which the rabbit pIgR is expressed in cultured canine epithelial cells (MDCK cells). These cells form a polarized monolayer when layered on permeable filter supports and allow us to reconstitute the transcytotic process in vitro. Two aspects of receptor function are currently being studied. First we have recently demonstrated that phosphorylation of the receptor on a single serine is required for its translocation across the epithelium, preliminary evidence suggests that this phosphorylation is catalyzed by a novel serine kinase and we are attempting to identify and characterize this kinase.

A further area of interest is in the development of the human intestinal barrier. We have recently defined an Fc-receptor for IgG on the surface of the human fetal intestine at 18-20 weeks1 gestation. This FcR has binding characteristics similar to the FcR found on the neonatal rodent intestine which is responsible for shuttling antibodies from maternal milk to the pup1s systemic circulation. We are further characterizing this receptor, particularly in relation to other human FcR1s its functional significance. In the last year, Dr. Walker has returned from a sabbatical at the Pasteur Institute where he has developed a human fetal intestinal cell line. Using this immortalized cell line he plans to pursue the role of intestinal epithelium in the mucosal immune response by determining what luminal stimuli effect expression of antigen presenting class I and II molecules, poly A receptor and cytokines.

Papers & Publications:

Chen C-C, Louie S, McCormick B, Walker WA, Shi H. Helminth-primed dendritic cells alter the host response to enteric bacterial infection. J Immunol 2006; 176:472-483.
Chen C-C, Louie S, McCormick B, Walker WA, Shi H. Concurrent infection of an intestinal helminth parasite impairs host resistance to Citrobacter rodentium and enhances Citrobacter-induced colitis mice. Infect Immun 2005; 73:5468-5481.
Rhee SJ, Walker WA, Cherayil BJ. Developmentally-regulated intestinal expression of IFNg and its target genes and the age-specific response to Salmonella infection. J Immunol 2005; 175:1127-1136.
Nanthakumar NN, Young C, Ko JS, Meng D, Chen J, Buie T, Walker WA. Glucocorticoid responsiveness in the developing human intestine: possible role in the prevention of necrotizing enterocolitis. AJP: GI and Liver Physiology 2005 288:G85-G92.