Interleukin-22 regulates B3GNT7 expression to induce fucosylation of glycoproteins in intestinal epithelial cells

Abstract

Interleukin (IL)-22 is a cytokine that plays a critical role in intestinal epithelial homeostasis. Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3). IL-22 signaling can induce transcription of genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and antimicrobial production. Recent studies have also implicated IL-22 signaling in the regulation of intestinal epithelial fucosylation in mice. However, whether IL-22 regulates intestinal fucosylation in human intestinal epithelial cells and the molecular mechanisms that govern this process are unknown. Here, in experiments performed in human cell lines and human-derived enteroids, we show that IL-22 signaling regulates expression of the B3GNT7 transcript, which encodes a β1-3-N-acetylglucosaminyltransferase that can participate in the synthesis of poly-N-acetyllactosamine (polyLacNAc) chains. Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins. Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins. Together, these data identify B3GNT7 as an intermediary in IL-22-dependent induction of fucosylation of glycoproteins and uncover a novel role for B3GNT7 in intestinal glycosylation. Interleukin (IL)-22 is a cytokine that plays a critical role in intestinal epithelial homeostasis. Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3). IL-22 signaling can induce transcription of genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and antimicrobial production. Recent studies have also implicated IL-22 signaling in the regulation of intestinal epithelial fucosylation in mice. However, whether IL-22 regulates intestinal fucosylation in human intestinal epithelial cells and the molecular mechanisms that govern this process are unknown. Here, in experiments performed in human cell lines and human-derived enteroids, we show that IL-22 signaling regulates expression of the B3GNT7 transcript, which encodes a β1-3-N-acetylglucosaminyltransferase that can participate in the synthesis of poly-N-acetyllactosamine (polyLacNAc) chains. Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins. Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins. Together, these data identify B3GNT7 as an intermediary in IL-22-dependent induction of fucosylation of glycoproteins and uncover a novel role for B3GNT7 in intestinal glycosylation. Glycosylation is a ubiquitous posttranslational modification that produces a diverse array of cellular glycans. Glycan assembly is complex, and the process is driven by transcriptional regulation of a portfolio of cellular “glycogenes,” the relative abundance of glycoprotein substrates, and availability of nucleotide sugar donor substrates. Glycans are synthesized in a sequential manner, where glycosyltransferases with distinct substrate specificities extend structures by transferring activated sugars to acceptor substrates in an α- or β-linkage, generating a glycan repertoire that is displayed on cell surfaces, secreted proteins, and within certain organelles. Glycans participate in the regulation of diverse biological processes, including proper protein folding and secretion, cellular adhesion and signaling, and immune cell trafficking (1Ohtsubo K. Marth J.D. Glycosylation in cellular mechanisms of health and disease.Cell. 2006; 126: 855-867Google Scholar, 2Moremen K.W. Tiemeyer M. Nairn A.V. Vertebrate protein glycosylation: Diversity, synthesis and function.Nat. Rev. Mol. Cell Biol. 2012; 13: 448-462Google Scholar, 3Neelamegham S. Mahal L.K. Multi-level regulation of cellular glycosylation: From genes to transcript to enzyme to structure.Curr. Opin. Struct. Biol. 2016; 40: 145-152Google Scholar). In the intestine, mucosal glycans are typically found attached to membrane-bound or secreted mucin-like glycoproteins through O-glycosidic linkages (O-glycosylation). GalNAc-type O-glycosylation begins in the Golgi apparatus with the transfer of N-acetylgalactosamine (GalNAc) to the hydroxyl group of a serine (Ser) or threonine (Thr) residue. This core structure can be elaborated into linear or branched structures. A common elaboration is the addition of poly-N-acetyllactosamine (polyLacNAc). polyLacNAc is a repeating copolymer of galactose (Gal) and N-acetylglucosamine (GlcNAc) produced by the concerted action of galactosyltransferases and GlcNAc-transferases. These extended O-glycans can be further decorated with sialic acid, fucose, sulfate groups, or ABO- or Lewis-type histo-blood group antigens, generating a wide diversity of possible structures (4Brockhausen I. Stanley P. O-GalNAc glycans.in: Varki A. Cummings R.D. Esko J.D. Stanley P. Hart G.W. Aebi M. Darvill A.G. Kinoshita T. Packer N.H. Prestegard J.H. Schnaar R.L. Seeberger P.H. Essentials of Glycobiology. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY2015: 113-123Google Scholar). For example, 6-sulfation of GlcNAc residues results in keratan sulfate II (KS II) structures (5Caterson B. Melrose J. Keratan sulfate, a complex glycosaminoglycan with unique functional capability.Glycobiology. 2018; 28: 182-206Google Scholar). Notably, mucosal O-glycans decorated with fucose have been identified as key regulators of both health and disease in the gut (6Goto Y. Uematsu S. Kiyono H. Epithelial glycosylation in gut homeostasis and inflammation.Nat. Immunol. 2016; 17: 1244-1251Google Scholar, 7Pickard J.M. Chervonsky A.V. Intestinal fucose as a mediator of host-microbe symbiosis.J. Immunol. 2015; 194: 5588-5593Google Scholar). L-fucose is a monosaccharide found in multiple classes of cell surface glycans. Incorporation of fucose into glycans is catalyzed by fucosyltransferases (FUTs). Thirteen human FUTs have been identified. FUTs catalyze the transfer of fucose from the guanosine diphosphate (GDP)—fucose donor to acceptor substrates in an α1-2-, α1-3-, α1-4- or α1-6-linkage, or α-linked to a serine or threonine side chain. Among these FUTs, ten are known to be involved in terminal fucosylation of glycan structures by decorating them with α1-2- (FUT1 and FUT2) or α1-3/4-linked fucose (FUT3–7 and FUT9–11) (8Becker D.J. Lowe J.B. Fucose: Biosynthesis and biological function in mammals.Glycobiology. 2003; 13: 41R-53RGoogle Scholar, 9Schneider M. Al-Shareffi E. Haltiwanger R.S. Biological functions of fucose in mammals.Glycobiology. 2017; 27: 601-618Google Scholar). Fucosylation is abundant in the mammalian gut and α1-2-fucosylation—primarily produced by Fut2—has emerged as a key regulator of commensal bacterial colonization and maintenance of bacterial symbiosis (10Pickard J.M. Maurice C.F. Kinnebrew M.A. Abt M.C. Schenten D. Golovkina T.V. Bogatyrev S.R. Ismagilov R.F. Pamer E.G. Turnbaugh P.J. Chervonsky A.V. Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness.Nature. 2014; 514: 638-641Google Scholar). Recent studies have explored the molecular mechanisms that control this process and implicate the interleukin (IL)-10 family member, IL-22, as the primary regulator of intestinal epithelial fucosylation in mice (10Pickard J.M. Maurice C.F. Kinnebrew M.A. Abt M.C. Schenten D. Golovkina T.V. Bogatyrev S.R. Ismagilov R.F. Pamer E.G. Turnbaugh P.J. Chervonsky A.V. Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness.Nature. 2014; 514: 638-641Google Scholar, 11Goto Y. Obata T. Kunisawa J. Sato S. Ivanov I.I. Lamichhane A. Takeyama N. Kamioka M. Sakamoto M. Matsuki T. Setoyama H. Imaoka A. Uematsu S. Akira S. Domino S.E. et al.Innate lymphoid cells regulate intestinal epithelial cell glycosylation.Science. 2014; 345: 1254009Google Scholar, 12Pham S. D. J.M. N. K. D.J. et fucosylation intestinal colonization to an 2014; Scholar). In the intestine, IL-22 is produced by 3 lymphoid cells H. family of lymphoid and of and tissue Immunol. Scholar). downstream function of IL-22 is mediated through of heterodimeric receptor of IL-22 receptor and S. J. J. Interleukin a novel human cytokine that through the and Biol. Scholar, E. H. S. of the functional receptor is a common of both the and IL-22 receptor Biol. which through activation of signal transducer and activator of transcription 3 D. S. the and in a cell that are with and distinct from Biol. Scholar). IL-22 signaling plays a critical role in maintenance of the intestinal epithelial by genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and induction of intestinal epithelial the of that the of IL-22 in intestinal whether IL-22 intestinal fucosylation in and the glycosyltransferases involved to be we that IL-22 signaling in human intestinal epithelial cells expression of the B3GNT7 transcript and of including mucosal glycans. also show that of B3GNT7 is sufficient to increased fucosylation of an by which intestinal fucosylation can be the of IL-22 signaling on expression in human intestinal epithelial we a of the human cell that and of the of the of the human intestinal cell Cell Scholar, S. S. T. I. P. M. D. are to as a of Cell Biol. 2017; Scholar). cells to of human IL-22 for and by In this IL-22 the expression of including with epithelial expression data (10Pickard J.M. Maurice C.F. Kinnebrew M.A. Abt M.C. Schenten D. Golovkina T.V. Bogatyrev S.R. Ismagilov R.F. Pamer E.G. Turnbaugh P.J. Chervonsky A.V. Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness.Nature. 2014; 514: 638-641Google Scholar, 11Goto Y. Obata T. Kunisawa J. Sato S. Ivanov I.I. Lamichhane A. Takeyama N. Kamioka M. Sakamoto M. Matsuki T. Setoyama H. Imaoka A. Uematsu S. Akira S. Domino S.E. et al.Innate lymphoid cells regulate intestinal epithelial cell glycosylation.Science. 2014; 345: 1254009Google Scholar, 12Pham S. D. J.M. N. K. D.J. et fucosylation intestinal colonization to an 2014; in of human cells with IL-22 to the induction of Additionally, IL-22 in expression of genes glycosyltransferases or regulators Among the genes by IL-22, induction of B3GNT7 the the by which IL-22 B3GNT7 we the data by found that B3GNT7 expression is by IL-22 in cells B3GNT7 expression as as IL-22 and further in B3GNT7 expression the IL-22 increased to whether B3GNT7 on activation of downstream IL-22 signaling, we cells with an or in of B3GNT7 expression in the of the the the of these we also which are from a of a K. H. A human cell that J. Scholar, J. B. Sato of the the of of human into the of the on the of in Scholar). IL-22-dependent induction of B3GNT7 expression also in cells cells with an or by IL-22 B3GNT7 expression increased by IL-22 in the of the the control to whether B3GNT7 expression on we cells with a of signaling Y. D. J. D. K. of as a of the signaling or that the IL-22-dependent in B3GNT7 expression also in the of in B3GNT7 transcript expression with the of we for this of be to whether IL-22 signaling also regulates B3GNT7 expression in we human enteroids, which are from intestinal These can be and of the from which J. In J. S.E. M. and intestinal intestinal and Biol. 2016; Scholar). that IL-22 in increased B3GNT7 expression in a human However, this the the of this we the lines from of which the in the the data show a in B3GNT7 expression in to IL-22 that IL-22 regulates expression of in and this expression S. D. J.M. N. K. D.J. et fucosylation intestinal colonization to an 2014; Scholar). intestinal epithelial tissue from mice expression in intestinal epithelial cells Y. M. intestinal regulates through and the 2017; we found that expression of in the the of these mice as with mice Together, these results that regulation of B3GNT7 expression to be in and mice and the also to in B3GNT7 expression the protein to B3GNT7 In IL-22 a and in intestinal epithelial fucosylation (10Pickard J.M. Maurice C.F. Kinnebrew M.A. Abt M.C. Schenten D. Golovkina T.V. Bogatyrev S.R. Ismagilov R.F. Pamer E.G. Turnbaugh P.J. Chervonsky A.V. Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness.Nature. 2014; 514: 638-641Google Scholar, 11Goto Y. Obata T. Kunisawa J. Sato S. Ivanov I.I. Lamichhane A. Takeyama N. Kamioka M. Sakamoto M. Matsuki T. Setoyama H. Imaoka A. Uematsu S. Akira S. Domino S.E. et al.Innate lymphoid cells regulate intestinal epithelial cell glycosylation.Science. 2014; 345: 1254009Google Scholar, 12Pham S. D. J.M. N. K. D.J. et fucosylation intestinal colonization to an 2014; Scholar). However, whether IL-22 also fucosylation in human intestinal epithelial cells been to the of IL-22 on we in to the fucosylation of glycoproteins from cell in of cells with for to of a that fucose, on of a that These as data that IL-22 expression and intestinal in mice in an Y. Obata T. Kunisawa J. Sato S. Ivanov I.I. Lamichhane A. Takeyama N. Kamioka M. Sakamoto M. Matsuki T. Setoyama H. Imaoka A. Uematsu S. Akira S. Domino S.E. et al.Innate lymphoid cells regulate intestinal epithelial cell glycosylation.Science. 2014; 345: 1254009Google Scholar). we in epithelial tissue from mice. with we found that expression in the of mice that expression in mice is also the also fucosylation in mice and to tissue in both and are in the intestine, and in of both of in the the of Together, these results and for the the for IL-22 signaling to regulate in both and human intestinal epithelial for multiple complex glycan that carbohydrate of 2006; Scholar). Lewis are the α1-3-fucosylated carbohydrate on cell P. Cummings R.D. common to glycans.in: Varki A. Cummings R.D. Esko J.D. Stanley P. Hart G.W. Aebi M. Darvill A.G. Kinoshita T. Packer N.H. Prestegard J.H. Schnaar R.L. Seeberger P.H. Essentials of Glycobiology. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY2015: Scholar). we the of IL-22 on Lewis expression in from in of cells to to expression of the Lewis X (Lex) increased in the of a of fucosylation A. P. K. A. of and fucosyltransferases the Biol. 2012; that increased on structures. whether expression also on IL-22 signaling, we also in the or of the or that the IL-22-dependent in expression of IL-22 signaling and that B3GNT7 also the the of IL-22 on the fucosylation of we performed a of human-derived from with and in cell surface fucosylation by IL-22 of from in increased of the which fucose in multiple linkages K. K. H. Y. K. M. Y. E. J. N. of a from A novel for core Biol. and of the IL-22 in increased to the the results to in availability and be Additionally, in glycosylation lines in subsequent experiments performed in in the can be displayed on and glycans attached to J. J.D. From cell adhesion to immune regulation and Biol. 2018; Scholar). whether the on or cells with structure of a from to glycans in cell K. J. molecular and functional of human S. A. on cells to with GalNAc-type the of the by the in molecular of a that is with to glycans levels by this and A and In to a and in levels and Together, these with the that IL-22 expression of known O-glycosylated glycoproteins implicate the of IL-22 in the transcriptional regulation and downstream fucosylation of O-glycosylated glycoproteins in human intestinal epithelial have to results the that IL-22 also fucosylation of mechanisms by which IL-22 induce increased the in in mice to increased expression Y. Obata T. Kunisawa J. Sato S. Ivanov I.I. Lamichhane A. Takeyama N. Kamioka M. Sakamoto M. Matsuki T. Setoyama H. Imaoka A. Uematsu S. Akira S. Domino S.E. et al.Innate lymphoid cells regulate intestinal epithelial cell glycosylation.Science. 2014; 345: 1254009Google we IL-22-dependent in expression of FUTs of of and genes FUTs primarily for synthesis A. P. B. and genes are in human IL-22-dependent in expression Additionally, of data and subsequent or IL-22 in expression of genes of genes involved in synthesis we possible mechanisms to for the in we that the in be to increased of glycan structures that are substrates for the that by IL-22 encodes an involved in the of polyLacNAc of keratan sulfate A. K. on keratan Scholar, K. Y. K. for synthesis of keratan sulfate Biol. which be to the we that cells with IL-22 increased with a that GlcNAc residues in both and polyLacNAc Y. S. J. H. J. of from the A J. Mol. 2017; Scholar). of the of also whether genes to polyLacNAc IL-22 expression of family in this cell of the family in these cells we performed experiments to the the in B3GNT7 expression and IL-22-dependent induction of intestinal we to expression of B3GNT7 in the in B3GNT7 expression we a and in IL-22-dependent expression and to whether epithelial fucosylation is by we the of B3GNT7 in cells and a in expression and we whether the in fucosylation on glycans. from cells from cells with IL-22, an in and Together, these data implicate B3GNT7 in the regulation of of glycans and to a in which the of is by the availability of glycans. In IL-22 signaling emerged as a key regulator of to in and and the subsequent induction of intestinal epithelial which regulates with (10Pickard J.M. Maurice C.F. Kinnebrew M.A. Abt M.C. Schenten D. Golovkina T.V. Bogatyrev S.R. Ismagilov R.F. Pamer E.G. Turnbaugh P.J. Chervonsky A.V. Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness.Nature. 2014; 514: 638-641Google Scholar, 12Pham S. D. J.M. N. K. D.J. et fucosylation intestinal colonization to an 2014; Scholar, H. S. P. Y. A. et glycosylation by the of the gut Scholar). However, whether IL-22 signaling regulates intestinal epithelial fucosylation in In with we IL-22-dependent regulation of expression and fucosylation and in human intestinal epithelial However, in the where IL-22 signaling regulates the synthesis of glycan structures decorated with α1-2- Y. Obata T. Kunisawa J. Sato S. Ivanov I.I. Lamichhane A. Takeyama N. Kamioka M. Sakamoto M. Matsuki T. Setoyama H. Imaoka A. Uematsu S. Akira S. Domino S.E. et al.Innate lymphoid cells regulate intestinal epithelial cell glycosylation.Science. 2014; 345: 1254009Google or fucose IL-22 signaling in human intestinal epithelial cells to the synthesis of α1-3-fucosylated glycan structures including the α1-3-fucosylated carbohydrate to the human histo-blood group and synthesis is primarily to the expression of and that catalyze the transfer of fucose to the acceptor GlcNAc in an A. P. B. and genes are in human Scholar, S. H. K. A. Y. T. Y. A. K. H. Lewis X expression in 2003; 13: Scholar). we expression of these genes in we to an IL-22-dependent regulation of and in both human and intestinal epithelium In we an IL-22-dependent regulation of B3GNT7 IL-22-dependent regulation of B3GNT7 in human intestinal cell in human-derived and also in that IL-22-dependent induction of B3GNT7 in which are to of the intestine, and in which are and to the S. S. T. I. P. M. D. are to as a of Cell Biol. 2017; the this be of further IL-22-dependent regulation of B3GNT7 in the a that be with that of the are in J.M. Chervonsky A.V. Intestinal fucose as a mediator of host-microbe symbiosis.J. Immunol. 2015; 194: 5588-5593Google Scholar, J. J.D. From cell adhesion to immune regulation and Biol. 2018; Scholar). However, IL-22-dependent regulation of B3GNT7 been in S. D. J.M. N. K. D.J. et fucosylation intestinal colonization to an 2014; Scholar). B3GNT7 encodes a β1-3-N-acetylglucosaminyltransferase that the transfer of GlcNAc from the diphosphate donor to acceptor substrates in a A. K. on keratan Scholar, K. N.H. A novel involved in of cells as in Scholar). B3GNT7 been to on glycans with the Among the acceptor glycans B3GNT7 the a glycan with on the residues A. K. on keratan Scholar). have that B3GNT7 is involved in the synthesis of keratan sulfate which is to to extend and polyLacNAc found in keratan sulfate A. K. on keratan Scholar, K. Y. K. for synthesis of keratan sulfate Biol. Scholar, R.D. B. H. M. K. Keratan sulfate in the 2018; Scholar). extend polyLacNAc B3GNT7 in with or galactosyltransferases to the repeating copolymer of and Notably, GlcNAc residues within polyLacNAc can as for terminal residues are for P. Cummings R.D. common to glycans.in: Varki A. Cummings R.D. Esko J.D. Stanley P. Hart G.W. Aebi M. Darvill A.G. Kinoshita T. Packer N.H. Prestegard J.H. Schnaar R.L. Seeberger P.H. Essentials of Glycobiology. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY2015: Scholar). the synthesis of carbohydrate structures the epitope a of we that IL-22 regulates the expression and of B3GNT7 to the availability of the acceptor that can be further by an as or this is in by the of B3GNT7 to regulate synthesis in the of IL-22 further are to the mechanisms of B3GNT7 possible that genes as of fucosylation by of the polyLacNAc acceptor a for the in fucose in the of FUTs in of Lewis are and human A. N. S. in human a role for enzyme cell Biol. Scholar). we that the relative abundance and of expression the of α1-3-fucosylated glycans produced in to results that of the epitope produced in to IL-22 is found on O-glycosylated intestinal glycoproteins the that is attached to glycans In the intestine, the O-glycosylated glycoproteins are H. of A of the 2012; Scholar). In mucosal fucose can be to a by of blood group or to GlcNAc by of Lewis (8Becker D.J. Lowe J.B. Fucose: Biosynthesis and biological function in mammals.Glycobiology. 2003; 13: 41R-53RGoogle generating a of glycan structures. can regulate commensal bacterial colonization by a for distinct D. N. glycan in the human gut 2015; Scholar, them or the intestinal the gut Scholar). For example, and common of the intestinal that can fucose from Lewis that glycans on mucosal glycans and this fucose as a to bacterial and colonization in the glycan and of a human gut bacterial Scholar, H. A. M. J. E. H. T. K. distinct from are for the of and Scholar, H. E. H. T. K. H. in the substrate specificities and structures of family from 2012; Scholar). However, a of that the of fucose on in intestinal homeostasis D. N. glycan in the human gut 2015; Scholar, them or the intestinal the gut of the molecular mechanisms that govern fucosylation is and is the of studies in Together, the results identify B3GNT7 as intermediary in the IL-22 induction of intestinal fucosylation of glycans. transcription of B3GNT7 and the subsequent synthesis of Lex-decorated glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins a novel role for B3GNT7 in intestinal glycosylation. have the of B3GNT7 in the synthesis of keratan sulfate in tissue R.D. B. H. M. K. Keratan sulfate in the 2018; Scholar). However, abundant expression in both K. N.H. A novel involved in of cells as in and human of B3GNT7 expression in and in the of 2014; intestinal a role for this enzyme in the regulation of intestinal glycosylation been identified. Notably, of B3GNT7 expression been to of cells of B3GNT7 expression in and in the of 2014; Scholar). of expression sulfate in mice M. S. I. D. J. T. H. A. E. Y. a novel that is in intestinal and in 2015; Scholar). the intestinal that regulate B3GNT7 expression and function whether of B3GNT7 can be to intestinal the intestinal to and in the from fucose from in from in from and from from for cell enzyme with cells in with and human cells in with and cell lines in a and cell for cell and Y. M. intestinal regulates through and the 2017; mice and as the of to and mice for of mice group as the to experiments performed by the and of the tissue by the and experiments on these to from the tissue of and tissue to the in and with for and for 3 in on for and the tissue in to the cell in and in a tissue in with the to be lines and for In also in the for the 3 to to to and lines for the experiments in in a tissue and A with for to the enteroids, of the with and with and for a further the addition of for In or control also to the addition of with IL-22 for and as M. epithelial A human for Scholar). in for cell in and into subsequent on for with the cell cells further with the or for by with and for also for for in a and the data the to and for experiments a of with cells in for to to cells in for to to in for cell for to the addition of to the In or control to the or control to the to the addition of cells a of with in for to to and in for to the addition of to the cells and and performed to B3GNT7 levels cells a of with in for to to and in for to the addition of and to the cytokine and performed to B3GNT7 levels from cells and to the where the and with as for and to from A. J. S. P. M. Scholar). Y. for to 2014; and the expression performed D.J. A for expression of expression Scholar). with of and from intestinal epithelial cell human enteroids, and intestinal tissue and for on a for human Cell for and experiments cells in of B3GNT7 human or and B3GNT7 or in the to cells for experiments into a tissue for cells for experiments in with and to for cytokine protein from cells with a a for For protein to of in for by and protein to a the Cell to the for with of from or from with an and in in with a and with in of and with or the substrate and in for with glycans protein from cells with of for and further O-glycosylated the by cytokine or to cells with and with in for and further of from as is a protein that of the and the S. A. 2017; Scholar). for and in the for in for in for 3 in for 3 in for 3 in for 3 and in for in in for and in and in to the and in the For and for in the of and the in and with and to for on Cell cells a of with in for to to in for to the addition of to the cells with and with for with and with in for in the For a with a of for in the and the cells with the into and to a with with and the with a on the Cell are as as in For cell or for of a by the a of data to This that have of with the of this Nairn and for for of and for on the Additionally, we to Schnaar and for D. J. and J. J. K. D. J. M. N. and M. data D. J. M. N. and A. K. H. and J. J. K. D. J. M. N. A. and M. D. J. and D. P. H. S. A. and J. J. K. and J. J. K. D. J. and J. J. K. D. J. M. N. D. M. A. and J. J. K. and by the to J. J. K. and to and the to J. J. K. and to M. N. B. by H. is an of the is the of the and the of the of

Topics & Concepts