Thu, 07 Aug 2008 21:46:31 BST CiteULike: AlfonsoVicenteSuarez's Kastelein http://www.citeulike.org/user/AlfonsoVicenteSuarez/author/Kastelein CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1387797 <i>Immunity, Vol. 19, No. 5. (November 2003), pp. 641-644.</i><br /><br />Originally the only known heterodimeric cytokine, IL-12 is now part of a family of five cytokines and shares important functions in the regulation of both innate and adaptive immunity with two of them, IL-23 and IL-27. Although initially these three cytokines were considered to have largely overlapping immunological functions, more recent studies, including two articles in this issue of Immunity ( and ), indicate that they mediate complex and well-differentiated functions. The IL-12 Family of Heterodimeric Cytokines: New Players in the Regulation of T Cell Responses Giorgio Trinchieri Stefan Pflanz Robert Kastelein Immunity, Vol. 19, No. 5. (November 2003), pp. 641-644. 2007-06-13T16:42:37-00:00 2003 Immunity 19 5 641 644 il-12-general http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1379003 <i>Proc Natl Acad Sci U S A, Vol. 95, No. 2. (20 January 1998), pp. 588-593.</i><br /><br />The discovery of sequence homology between the cytoplasmic domains of Drosophila Toll and human interleukin 1 receptors has sown the conviction that both molecules trigger related signaling pathways tied to the nuclear translocation of Rel-type transcription factors. This conserved signaling scheme governs an evolutionarily ancient immune response in both insects and vertebrates. We report the molecular cloning of a class of putative human receptors with a protein architecture that is similar to Drosophila Toll in both intra- and extracellular segments. Five human Toll-like receptors--named TLRs 1-5--are probably the direct homologs of the fly molecule and, as such, could constitute an important and unrecognized component of innate immunity in humans. Intriguingly, the evolutionary retention of TLRs in vertebrates may indicate another role--akin to Toll in the dorsoventralization of the Drosophila embryo--as regulators of early morphogenetic patterning. Multiple tissue mRNA blots indicate markedly different patterns of expression for the human TLRs. By using fluorescence in situ hybridization and sequence-tagged site database analyses, we also show that the cognate Tlr genes reside on chromosomes 4 (TLRs 1, 2, and 3), 9 (TLR4), and 1 (TLR5). Structure prediction of the aligned Toll-homology domains from varied insect and human TLRs, vertebrate interleukin 1 receptors and MyD88 factors, and plant disease-resistance proteins recognizes a parallel beta/alpha fold with an acidic active site; a similar structure notably recurs in a class of response regulators broadly involved in transducing sensory information in bacteria. A family of human receptors structurally related to Drosophila Toll. FL Rock G Hardiman JC Timans RA Kastelein JF Bazan Proc Natl Acad Sci U S A, Vol. 95, No. 2. (20 January 1998), pp. 588-593. 2007-06-11T17:03:38-00:00 1998 Proc Natl Acad Sci U S A 0027-8424 95 2 588 593 tlr5-flagellin