LECLAIR, E. E.; NOMELLINI, V.; BAHENA, M.; BINGLE, C.D.; DePaul University; University of Sheffield: Innate Immunity in the Oral Cavity? A Mouse Tongue Tale

Epithelial surfaces are patrolled by molecules that recognize bacterial byproducts to enhance host defense. We describe the cloning and expression of a mouse gene, which we call TPL, whose mRNA appears strongly in the dorsal papillary surface of the tongue. Expression appears postnatally (~2 days) and persists to old age (> 2 yrs). Strikingly, expression is limited to the “valleys” between tongue papillae, suggesting that separate columns of interpapillary cells initiate TPL expression as they differentiate dorsally. Several lines of evidence position TPL as a putative defense compound: 1) Structure: Amino acids of TPL are 60% identical to mouse PLUNC, a small secreted protein upregulated in epithelial surfaces of the nose and lungs. 2) Protein structure: The solved 3D structure of human PLUNC puts it in a class with lipid binding protein (LBP) and bacterial permeability increasing protein (BPI), two signaling factors in the human response to bacteria (see Hum Mol Genet 2002:937-43). 3) Genomic organization: Mouse genome data show that PLUNC and TPL have similar introns/exons, and are found clustered with related genes on mouse chromosome 2, suggesting multiple gene duplications. No homologs were detected in Drosophila, C. elegans or Fugu genomes. 4) Expression pattern: We show that TPL, PLUNC and a related gene, VEG (Von Ebner minor salivary gland protein) are expressed in complex overlapping domains on epithelial surfaces of the mouse tongue, nose, lungs, pharynx and palate, among other locations. These data are consistent with the hypothesis that PLUNC, TPL and related molecules are mammalian host defense molecules that may protect epithelial surfaces from potentially pathogenic microorganisms. Suported by NHBLI & the American Lung Association (EEL) and funds from the Wellcome Trust (CDB).