Characterization of a Novel C-type Lectin-like Gene, LSECtin

A new C-type lectin-like gene encodes 293 amino acids and maps to chromosome 19p13.3 adjacent to the previously described C-type lectin genes, CD23, dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), and DC-SIGN-related protein (DC-SIGNR). The four genes form a tight cluster in an insert size of 105 kb and have analogous genomic structures. The new C-type lectin-like molecule, designated liver and lymph node sinusoidal endothelial cell C-type lectin (LSECtin), is a type II integral membrane protein of ∼40 kDa in size with a single C-type lectin-like domain at the COOH terminus, closest in homology to DC-SIGNR, DC-SIGN, and CD23. LSECtin mRNA was only expressed in liver and lymph node among 15 human tissues tested, intriguingly neither expressed on hematopoietic cell lines nor on monocyte-derived dendritic cells (DCs). Moreover, LSECtin is expressed predominantly by sinusoidal endothelial cells of human liver and lymph node and co-expressed with DC-SIGNR. LSECtin binds to mannose, GlcNAc, and fucose in a Ca2+-dependent manner but not to galactose. Our results indicate that LSECtin is a novel member of a family of proteins comprising CD23, DC-SIGN, and DC-SIGNR and might function in vivo as a lectin receptor. A new C-type lectin-like gene encodes 293 amino acids and maps to chromosome 19p13.3 adjacent to the previously described C-type lectin genes, CD23, dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), and DC-SIGN-related protein (DC-SIGNR). The four genes form a tight cluster in an insert size of 105 kb and have analogous genomic structures. The new C-type lectin-like molecule, designated liver and lymph node sinusoidal endothelial cell C-type lectin (LSECtin), is a type II integral membrane protein of ∼40 kDa in size with a single C-type lectin-like domain at the COOH terminus, closest in homology to DC-SIGNR, DC-SIGN, and CD23. LSECtin mRNA was only expressed in liver and lymph node among 15 human tissues tested, intriguingly neither expressed on hematopoietic cell lines nor on monocyte-derived dendritic cells (DCs). Moreover, LSECtin is expressed predominantly by sinusoidal endothelial cells of human liver and lymph node and co-expressed with DC-SIGNR. LSECtin binds to mannose, GlcNAc, and fucose in a Ca2+-dependent manner but not to galactose. Our results indicate that LSECtin is a novel member of a family of proteins comprising CD23, DC-SIGN, and DC-SIGNR and might function in vivo as a lectin receptor. Protein-carbohydrate interactions serve multiple functions in the immune system. A number of animal lectins (sugar-binding proteins) mediate both pathogen recognition and cell-cell interactions using structurally related Ca2+-dependent carbohydrate-recognition domains (C-type CRDs) 1The abbreviations used are: CRD, carbohydrate recognition domain; BSA, bovine serum albumin; CTLD, C-type lectin-like domain; DC, dendritic cell(s); DC-SIGN, DC-specific ICAM-3-grabbing nonintegrin; DC-SIGNR, DC-SIGN-related protein; EST, expressed sequence tag; FCS, fetal cattle serum; FACS, fluorescence-activated cell sorting; ICAM, intercellular adhesion molecule; ORF, open reading frame; PBMC, peripheral blood monocyte cell; RACE, rapid amplification of cDNA ends; CHO, Chinese hamster ovary; aa, amino acids; Ab, antibody; mAb, monoclonal antibody; contig, group of overlapping clones; LSECtin, liver and lymph node sinusoidal endothelial cell C-type lectin; sLSECtin, soluble LSECtin. (1Weis W.I. Taylor M.E. Drickamer K. Immunol. Rev. 1998; 163: 19-34Google Scholar). There are two groups of membrane-bound C-type lectins, type I and type II C-type lectins, which are distinguished from each other by the orientation of their cell surface NH2 terminus pointing outwards or into the cytoplasm of the cell, respectively. The type II C-type lectins identified so far have a single CRD at the extracellular carboxyl terminus (2Figdor C.G. van Kooyk Y. Adema G.J. Nat. Immunol. Rev. 2002; 2: 77-84Google Scholar). The genes coding for the type II C-type lectins are mainly localized in chromosome 12p12.3-p13.2 (3Trowsdale J. Barten R. Haude A. Stewart C.A. Beck S. Wilson M.J. Immunol. Rev. 2001; 181: 20-38Google Scholar) and 19p13.3 (4Soilleux E.J. Barten R. Trowsdale J. J. Immunol. 2000; 165: 2937-2942Google Scholar). The former is the natural killer gene complex, and the latter is the cluster of genes including CD23, dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), and DC-SIGN-related protein (DC-SIGNR). In the last cluster, these three genes have analogous genomic structures and form a tight cluster in an insert size of 105 kb on human chromosome 19p13.3 (4Soilleux E.J. Barten R. Trowsdale J. J. Immunol. 2000; 165: 2937-2942Google Scholar). They display similar domain composition and organization containing a short NH2-terminal cytoplasmic tail, a transmembrane region, and an extracellular region that consists of a coiled-coil neck domain and a C-terminal CRD. The close linkage and similar genomic and protein structures suggest that these three genes may have arisen via duplication of an ancestral gene (5Soilleux E.J. Clin. Sci. 2003; 104: 437-446Google Scholar). Indeed, they share some common functions in vivo in that they serve as cell-cell adhesion molecules and play an important role in the immune system (6Bonnefoy J.Y. Lecoanet-Henchoz S. Gauchat J.F. Graber P. Aubry J.P. Jeannin P. Plater-Zyberk C. Int. Rev. Immunol. 1997; 16: 113-128Google Scholar, 7Van Kooyk Y. Geijtenbeek T.B. Immunol. Rev. 2002; 186: 47-56Google Scholar, 8Bashirova A.A. Geijtenbeek T.B. van Duijnhoven G.C.F. van Vliet S.J. Eilering J.B.G. Martin M.P. Wu L. Martin T.D. Viebig N. Knolle P.A. KewalRamani V.N. van Kooyk Y. Carrington M. J. Exp. Med. 2001; 193: 671-678Google Scholar). CD23, a low affinity receptor for IgE, was first identified as a type II C-type lectin in the latter gene cluster, which was expressed on a wide variety of human hematopoietic cell types including B and T cells, follicular dendritic cells, monocytes, platelets, Langerhans cells, esoinophils, and natural killer cells (9Conrad D.H. Annu. Rev. Immunol. 1990; 8: 623-645Google Scholar). CD23 specifically recognizes at least four different ligands, including IgE (10Yukawa K. Kikutani H. Howaki H. Yamasaki K. Yokota A. Nakamura H. Barsumian E.L. Hardy R.R. Suemura M. Kishimoto T. J. Immunol. 1987; 38: 2576-2580Google Scholar), CD21 (11Aubry J.P. Pochon S. Gauchat J.F. Nueda-Marin A. Holers V.M. Graber P. Siegfried C. Bonnefoy J.Y. J. Immunol. 1994; 152: 5806-5813Google Scholar), CD18/CD11b, and CD18/CD11c β2-integrins (12Lecoanet-Henchoz S. Gauchat J.F. Aubry J.P. Graber P. Life P. Paul-Eugene N. Ferrua B. Corbi A.L. Daugs B. Plater-Zyberk C. Bonnefoy J.Y. Immunity. 1995; 3: 119-125Google Scholar). The and interactions are lectin-like in that CD23 recognizes carbohydrate structures expressed on CD21 and (11Aubry J.P. Pochon S. Gauchat J.F. Nueda-Marin A. Holers V.M. Graber P. Siegfried C. Bonnefoy J.Y. J. Immunol. 1994; 152: 5806-5813Google Scholar, S. Gauchat J.F. Aubry J.P. Graber P. Life P. Paul-Eugene N. Ferrua B. Corbi A.L. Daugs B. Plater-Zyberk C. Bonnefoy J.Y. Immunity. 1995; 3: 119-125Google Scholar). In CD23 binds IgE, the recognition of a protein a M. Wu S. M. Immunol. Rev. Scholar). CD23 an important role in a variety of as cell-cell of B cells in of IgE and (6Bonnefoy J.Y. Lecoanet-Henchoz S. Gauchat J.F. Graber P. Aubry J.P. Jeannin P. Plater-Zyberk C. Int. Rev. Immunol. 1997; 16: 113-128Google Scholar). DC-SIGN, described in as a C-type lectin to the human surface S. Sci. S. A. Scholar), is expressed on dendritic cells and some of T.B. R. van Vliet S.J. van Duijnhoven Adema G.J. van Kooyk Y. C.G. 2000; Scholar, E.J. J. Trowsdale J. N. B. J. 2002; Scholar). DC-SIGNR, which to at the is expressed on human liver and lymph node sinusoidal and endothelial cells A.A. Geijtenbeek T.B. van Duijnhoven G.C.F. van Vliet S.J. Eilering J.B.G. Martin M.P. Wu L. Martin T.D. Viebig N. Knolle P.A. KewalRamani V.N. van Kooyk Y. Carrington M. J. Exp. Med. 2001; 193: 671-678Google Scholar, S. E.J. G.J. Trowsdale J. B. N. Sci. S. A. 2001; Scholar). of and DC-SIGNR are C-type lectins in that they and related their Drickamer K. J. 2001; Scholar). the of dendritic cells and their with interactions with on and on T cells, T.B. R. van Vliet S.J. van Duijnhoven Adema G.J. van Kooyk Y. C.G. 2000; Scholar, T.B. van Vliet S.J. van Duijnhoven R. C.G. van Kooyk Y. Nat. Immunol. 2000; Scholar). DC-SIGNR binds to on T cells and is in liver sinusoidal endothelial cells interactions with A.A. Geijtenbeek T.B. van Duijnhoven G.C.F. van Vliet S.J. Eilering J.B.G. Martin M.P. Wu L. Martin T.D. Viebig N. Knolle P.A. KewalRamani V.N. van Kooyk Y. Carrington M. J. Exp. Med. 2001; 193: 671-678Google Scholar, S. E.J. G.J. Trowsdale J. B. N. Sci. S. A. 2001; Scholar). have that and DC-SIGNR of and including human T.B. R. van Vliet S.J. van Duijnhoven J. KewalRamani V.N. C.G. van Kooyk Y. 2000; Scholar), J. Corbi A.L. R. J. 2002; Scholar), A. H. M. T. C. J.F. J. Immunity. 2002; Scholar), H. A. S. A. C. R. J. 2003; Scholar), and L. M. A. L. B. J. Exp. Med. 2003; Scholar, T.B. Vliet S.J. M. B. Kooyk Y. J. Exp. Med. 2003; Scholar), in which and related on of these play a role in their new genes with important functions have on of human fetal liver cDNA in C.G. Y. Wu 2001; Scholar, H. Y. H. Wu Y. Y. S. M. J. 2002; Scholar, C. Y. S. M. H. J. C. Y. L. Wu C. S. 2000; Scholar). novel adhesion expressed sequence of human fetal liver cDNA Y. C. Wu S. H. C. Y. J. S. L. S. K. Y. Wu C. 2001; Scholar) have to of CD23, DC-SIGN, and DC-SIGNR, which as of are important adhesion molecules in these an insert with homology to human DC-SIGNR, DC-SIGN, and CD23 at the amino was for novel C-type lectin-like LSECtin, is localized CD23 and DC-SIGN, which is by DC-SIGNR, on chromosome and these four structurally related genes form a tight In on the of LSECtin, and of cell the the monocyte cell lines and the B cell lines and the T cell lines and the natural killer cell and liver cell lines and from the of Chinese of The cell was from the cell lines in with and and cells in with FCS, and endothelial cells as previously J. P. van R. J. J.F. Scholar). blood cells from by of these for with blood from by from peripheral blood as described N. S. A. B. J. Exp. Med. 1994; Scholar). In in to to at the cells by with and the in with and the by with and at and and by for and and of novel adhesion molecules to CD23, DC-SIGN, and DC-SIGNR, a cDNA of human fetal liver of in Y. C. Wu S. H. C. Y. J. S. L. S. K. Y. Wu C. 2001; Scholar) was using the with their CRD A novel human cDNA to human DC-SIGNR, DC-SIGN, and CD23 was and was the and using the and the human to for on the results of an and a to and respectively. and using a cDNA amplification on from of from fetal liver and by as described by the In both a was with an for and for respectively. at for by at for for and for The into for was on an Life and of cDNA sequence of LSECtin was used to the human and genomic The the cDNA and genomic sequence was to the of and and the of the LSECtin The genomic of DC-SIGN, DC-SIGNR, and CD23 using their cDNA for The sequence among the type II C-type lectins to LSECtin was using the was identified using the on the at of the protein was with the that was used to a of and their and human multiple containing of to the of LSECtin and the in containing cDNA for LSECtin or The for LSECtin to the open reading of LSECtin and was with the of I and using the system the to at with an from human peripheral blood cells, cell and fetal liver using cDNA was using and as by the the of LSECtin used for The the at for and at for at for and at for for used as an for cDNA as as The on of coding the extracellular LSECtin was by with the into and The the neck and domain of LSECtin was of the sequence in was into protein was from cells in and using protein was to and the protein was from the and with an of J. T. A Scholar). The LSECtin was into four of with serum was and from the these first with cells which was by of cells with for 15 on J. T. A Scholar), and with cells, which with and with The of was by an A The of serum was and as and coding region of LSECtin was by on the fetal liver as described into and The coding sequence of LSECtin was into to the the of C-terminal cells with of using and for in of for cells LSECtin and in with cells LSECtin and cells with an in a containing and a of by or by and which with serum or an with or and with the system LSECtin protein in fetal the membrane proteins from fetal liver using an system to previously Scholar). The membrane and and of fetal liver tissues by and as described on in with bovine serum for at and with or to the A Scholar). cell on an and cells from using in 105 cells in containing BSA, and or at the cells with the and in of containing of or for at with and by a of human liver and lymph node tissues from at the of for in the in for and in serum for the with serum and for at respectively. with for and with to for was using and the with was on liver and lymph node tissues using serum and was as described in bovine serum both at with and for at with or with The by using a of containing the extracellular region of LSECtin to the region of human by using fetal liver The and used and The was of the sequence of in S. 1995; Scholar). into cells by The cells by as described of in a with the was by affinity with A and by with as previously L. S. Taylor M.E. J. 2002; Scholar). of in of and was of or The was and the with of by of and cells, cells in and was on for at and and the was of was to of and and to the The in and in and by with of and of for on and for at The in and in of by and by with was with using to the by the proteins on by of at of the using in and for at the for at with containing BSA, and three with to of was to for at the with was by for 15 and by The was at on a of that of for each by the to the for of LSECtin a of the C-type novel adhesion molecules of the C-type lectin the expressed of the cDNA of human fetal liver in was with the CRD domains of CD23, DC-SIGN, and DC-SIGNR. novel which is and a domain and was and to overlapping sequence identified from the liver and in a of the cDNA of the new and on human fetal liver two on the terminus and of the terminus The cDNA of the new gene was and an from to that a with a of The is by and and by a sequence that a with the by M. Scholar) for In the terminus of the sequence a by a of the amino sequence of the new gene of type II integral membrane an at the NH2 terminus and a short cytoplasmic of a transmembrane domain The extracellular of is of a region of that the transmembrane domain to a single in the COOH terminus at least There are two localized in the region The protein using the amino sequence of to an to which was from by using the gene and homology with including protein DC-SIGNR CD23 and of and DC-SIGNR as as other of CD23 Moreover, using the domain of the new for the protein to the to DC-SIGNR, to DC-SIGN, and to CD23. on the new gene to type II C-type lectins DC-SIGNR, DC-SIGN, and CD23 and expressed in liver and lymph node sinusoidal endothelial cells was LSECtin and lymph node sinusoidal endothelial cell C-type the among LSECtin, DC-SIGNR, DC-SIGN, and CD23, a with their that the of LSECtin of the and of the amino used to C-type lectins K. 3: Scholar). The of LSECtin of the amino for and two of four for an that in other C-type lectins K. Scholar) is in the of LSECtin. LSECtin to the type II lectin-like receptor gene family and may function as a lectin receptor. The neck of LSECtin four similar to that of CD23, which and coiled-coil and the of in CD23 (9Conrad D.H. Annu. Rev. Immunol. 1990; 8: 623-645Google Scholar). is important to that the of LSECtin sequence in a manner similar to of CD23 as a (6Bonnefoy J.Y. Lecoanet-Henchoz S. Gauchat J.F. Graber P. Aubry J.P. Jeannin P. Plater-Zyberk C. Int. Rev. Immunol. 1997; 16: 113-128Google Scholar) and may a novel suggest that in the CTLD, LSECtin is similar to and DC-SIGNR to CD23, but in the neck region and cytoplasmic tail, LSECtin is analogous to CD23 to and DC-SIGNR. The LSECtin on 19p13.3 and a with CD23, DC-SIGN, and the cDNA of LSECtin was the human genomic using the genomic sequence was The cDNA of LSECtin chromosome to the LSECtin cDNA and genomic sequence that LSECtin gene and consists of The of the with the of the and The human genomic was by of DC-SIGNR, DC-SIGN, and CD23, which to an insert size of 105 kb of 19p13.3 (4Soilleux E.J. Barten R. Trowsdale J. J. Immunol. 2000; 165: 2937-2942Google Scholar). to DC-SIGNR, DC-SIGN, LSECtin, and CD23 are in and form a tight DC-SIGN, LSECtin, and CD23 are in the but DC-SIGNR is in to The genomic of the four C-type lectin genes that they have analogous genomic organization for their neck is of type II C-type lectins K. Scholar), the to their are by three at the terminus, and their cytoplasmic and are by two In their neck the number and the of are different among The of LSECtin in the neck region is similar to that of CD23 to that of and DC-SIGNR. There are four in the neck region of LSECtin and in that of CD23, and and of LSECtin to and of CD23 in respectively. In of LSECtin to and of CD23, both of in a In to CD23 and LSECtin, is only containing in the neck region of both and DC-SIGNR (4Soilleux E.J. Barten R. Trowsdale J. J. Immunol. 2000; 165: 2937-2942Google Scholar). The close linkage and similar genomic structures suggest that these four genes may have arisen from an ancestral gene via of LSECtin LSECtin protein was by with a to the extracellular region of LSECtin or and a of ∼40 kDa in the of cells LSECtin but not in cells with the The size is that from the amino sequence of LSECtin a to LSECtin two and in the neck region similar to DC-SIGNR, DC-SIGN, and CD23, of which are results suggest that the serum is to LSECtin. The neck region of LSECtin was to a coiled-coil and might form in a manner similar to that of CD23, which the of the of cells LSECtin by or and to with and but they to a single to results suggest that LSECtin may in as a A of an was LSECtin a II of amino sequence of LSECtin that is a type II integral membrane protein as described LSECtin expressed on the cell a of cells a protein of LSECtin was with LSECtin or for in the cells using both serum and was with the the surface of LSECtin protein on cells was by using or cells with these two that human LSECtin protein is on the cell surface and to a type II integral membrane protein only recognizes the C-terminal region and cells with LSECtin. of human LSECtin protein in fetal was from fetal liver and the membrane was using the system Scholar). that a was in the membrane but not in cytoplasm and cell by with that LSECtin is a membrane protein in fetal and of an to the of LSECtin two human multiple to the to the of LSECtin. that is of a size that is with the cDNA by The is expressed specifically in human fetal and lymph node but not in peripheral blood and the of LSECtin that of DC-SIGNR for S. E.J. G.J. Trowsdale J. B. N. Sci. S. A. 2001; Scholar). LSECtin gene in fetal and lymph node into that may expressed by hematopoietic cells, so first different hematopoietic cell lines or cell lines from liver that LSECtin was neither expressed by nor cell lines nor by peripheral blood and The liver cell and of LSECtin from of LSECtin B and and human endothelial cells for of LSECtin, is an to LSECtin from In on from fetal liver a of to the of LSECtin. LSECtin was not expressed by hematopoietic cell lines as as results suggest that the of LSECtin may similar to that for DC-SIGNR other CD23 and which cell LSECtin in with of human liver and lymph node using LSECtin was on the lymph node A and and on the the of the liver and in the of was The the endothelial cell-specific human a similar on liver and lymph node and S. C. Clin. Scholar) and the of the cells as endothelial DC-SIGNR is expressed in both liver sinusoidal endothelial cells and lymph node sinusoidal endothelial cells S. E.J. G.J. Trowsdale J. B. N. Sci. S. A. 2001; Scholar). the that LSECtin and DC-SIGNR may co-expressed in the cells, of lymph node A and and liver and was using both and two similar and and results that LSECtin and DC-SIGNR are co-expressed by liver and lymph node sinusoidal endothelial is co-expressed with DC-SIGNR on the sinusoidal endothelial cells of liver and lymph A and of lymph node with serum and serum A and B and of liver with and and was of of that LSECtin with and including and the of LSECtin LSECtin was as protein to the of human expressed in cells, and for to In these with protein in with the with containing to proteins to the in a Ca2+-dependent A of was on of and but not on and in the of results that LSECtin for and as as The of LSECtin in was by LSECtin on The cell was on the and with LSECtin was to and which LSECtin binds a in which for of to protein was the which only a of of different to LSECtin. are in with in In with the results of the mannose, GlcNAc, and fucose of to and of and to LSECtin is of The of to and to are The with is to to with the of the not of of with other C-type lectins Drickamer K. J. 2001; Scholar, Drickamer K. W.I. J. Scholar). The results suggest that LSECtin, and DC-SIGNR, different recognition of the and and the have an at these Drickamer K. J. 2001; Scholar). In with and DC-SIGNR that for Drickamer K. J. 2001; Scholar), at the not with and with the as as of to protein by using the are with the to the to protein for each using the are as of in in a new a novel C-type lectin LSECtin, adjacent to the previously described type II C-type lectins, CD23, DC-SIGN, and DC-SIGNR. The amino sequence of LSECtin the of to CD23, DC-SIGN, and DC-SIGNR. the of among not to at the amino their protein domain composition and similar genomic organization with the that they are from a common which and to to the four genes with and common The of LSECtin in C-terminal CTLD, a function that may to The with in C-type lectin domains in the that into with the for the of and In the CRD, in and to the K. 3: Scholar). for of the of LSECtin are but is only in a similar manner to human CD23 as as other L. S. Taylor M.E. J. 2002; Scholar, Taylor M.E. J. 1997; Scholar, M.J. A.A. C. B. Scholar, C. S. D.H. 1994; Scholar). In an of is in LSECtin, but an is in human CD23 (9Conrad D.H. Annu. Rev. Immunol. 1990; 8: 623-645Google Scholar). The of the sequence at the to the of DC-SIGN, DC-SIGNR, and other C-type lectins K. Scholar) that LSECtin with and In with the LSECtin mannose, and in a Ca2+-dependent manner but not galactose. DC-SIGNR, LSECtin affinity for for fucose Drickamer K. J. 2001; Scholar). DC-SIGNR to from other C-type lectins in that affinity for multiple as T.B. R. van Vliet S.J. van Duijnhoven J. KewalRamani V.N. C.G. van Kooyk Y. 2000; Scholar), T.B. van Duijnhoven van Vliet S.J. C.G. van Kooyk Y. J. 2002; Scholar), and H. A. S. A. C. R. J. 2003; Scholar) and recognizes an a H. Drickamer K. W.I. 2001; Scholar). C-type lectins share an and a affinity for their in carbohydrate and of carbohydrate recognition The of to LSECtin to the of are similar to of DC-SIGNR, the that the of LSECtin and DC-SIGNR for may different in vivo In CD23 with IgE in recognition (9Conrad D.H. Annu. Rev. Immunol. 1990; 8: 623-645Google Scholar), LSECtin to a protein may and are to LSECtin not only Ca2+-dependent to a of similar to DC-SIGNR but analogous to DC-SIGNR. of co-expressed by sinusoidal endothelial cells in liver and lymph LSECtin was not on hematopoietic cells in a manner similar to DC-SIGNR A.A. Geijtenbeek T.B. van Duijnhoven G.C.F. van Vliet S.J. Eilering J.B.G. Martin M.P. Wu L. Martin T.D. Viebig N. Knolle P.A. KewalRamani V.N. van Kooyk Y. Carrington M. J. Exp. Med. 2001; 193: 671-678Google Scholar). DC-SIGNR, which is expressed on a of the S. E.J. G.J. Trowsdale J. B. N. Sci. S. A. 2001; Scholar), LSECtin was not in by or of LSECtin in other tissues not the of or may in other sinusoidal endothelial cells share some with lymph node sinusoidal endothelial lymph node and liver sinusoidal endothelial cells M. K. A Scholar, Y. J. Scholar) and Y. B. K. K. 1998; Scholar). the other both of with and with and the of interactions Y. B. K. K. 1998; Scholar, P.A. Immunol. Rev. 2000; Scholar). system a role in of both from blood and lymph with lectin have identified on both lymph node and liver sinusoidal endothelial cells (2Figdor C.G. van Kooyk Y. Adema G.J. Nat. Immunol. Rev. 2002; 2: 77-84Google Scholar). DC-SIGNR and the receptor type I C-type DC-SIGNR might mediate the of proteins from the in a manner similar to on in The role of DC-SIGNR to in the adhesion of T cells by with on T cells and for of some A.A. Geijtenbeek T.B. van Duijnhoven G.C.F. van Vliet S.J. Eilering J.B.G. Martin M.P. Wu L. Martin T.D. Viebig N. Knolle P.A. KewalRamani V.N. van Kooyk Y. Carrington M. J. Exp. Med. 2001; 193: 671-678Google Scholar, S. E.J. G.J. Trowsdale J. B. N. Sci. S. A. 2001; Scholar). specifically recognizes and binds to mannose, or in a Ca2+-dependent are not at the of carbohydrate of cells but are on the of L. 2002; Scholar). A novel role for on lymph node sinusoidal endothelial cells is to T cells and lymph H. E.L. R. K. M. S. J. Exp. Med. 2001; Scholar). The and of LSECtin a role for receptor in as as in cell-cell as have for DC-SIGNR and Indeed, LSECtin to T cells, and by both and L. H. Y. L. Y. and of the role of the of natural into the of lectin have the of of the of liver and lymph node sinusoidal endothelial cells in cell-cell adhesion and are to for of human liver and lymph node P. R. for the of the and Taylor for on the and and for and of the