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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chaudhary, P. M. Articles by Nelson, P. S. Search for Related Content PubMed PubMed Citation Articles by Chaudhary, P. M. Articles by Nelson, P. S. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Cloning and Characterization of Two Toll/Interleukin-1 Receptor-Like Genes TIL3 and TIL4: Evidence for a Multi-Gene Receptor Family in Humans Preet M. Chaudhary, Camari Ferguson, Vilaska Nguyen, Oanh Nguyen, Hillary F. Massa, Michael Eby, Alan Jasmin, Barbara J. Trask, Leroy Hood, and Peter S. Nelson From the Department of Medicine and Molecular Biotechnology, University of Washington, Seattle, WA. Remarkable structural and functional similarities exist between the Drosophila Toll/Cactus/Dorsal signaling pathway and the mammalian cytokine-mediated interleukin-1 receptor (IL-1R)/I-B/NF-B activation cascade. In addition to a role regulating dorsal-ventral polarity in the developing Drosophila embryo, signaling through Drosophila Toll (dToll) activates the nonclonal, or innate, immune response in the adult fly. Recent evidence indicates that a human homologue of the dToll protein participates in the regulation of both innate and adaptive human immunity through the activation of NF-B and the expression of the NF-B-controlled genes IL-1, IL-6, and IL-8, thus affirming the evolutionary conservation of this host defense pathway. We report here the cloning of two novel human genes, TIL3 and TIL4 (Toll/IL-1R-like-3, -4) that exhibit homology to both the leucine-rich repeat extracellular domains and the IL-1R-like intracellular domains of human and Drosophila Toll. Northern analysis showed distinctly different tissue distribution patterns with TIL3 expressed predominantly in ovary, peripheral blood leukocytes, and prostate, and TIL4 expressed primarily in peripheral blood leukocytes and spleen. Chromosomal mapping by fluorescence in situ hybridization localized the TIL3 gene to chromosome 1q41-42 and TIL4 to chromosome 4q31.3-32. Functional studies showed that both TIL3 and TIL4 are able to activate NF-B, though in a cell type-dependent fashion. Together with human Toll, TIL3 and TIL4 encode a family of genes with conserved structural and functional features involved in immune modulation. Blood, Vol. 91 No. 11 (June 1), 1998: pp. 4020-4027 © 1998 by The American Society of Hematology. 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