Exploiting the neonatal crystallizable fragment receptor to treat kidney disease DOI Creative Commons
James Dylewski, George Haddad, Judith Blaine

et al.

Kidney International, Journal Year: 2023, Volume and Issue: 105(1), P. 54 - 64

Published: Oct. 29, 2023

The neonatal crystallizable fragment receptor (FcRn) was initially discovered as the that allowed passive immunity in newborns by transporting maternal IgG through placenta and enterocytes. Since its initial discovery, FcRn has been found to exist throughout all stages of life many different cell types. Beyond immunity, is necessary for intrinsic albumin recycling important antigen processing presentation. Given multiple roles, used disease treatments including a new class agents were developed inhibit treatment variety autoimmune diseases. Certain populations within kidney also express high levels this receptor. Specifically, podocytes, proximal tubule epithelial cells, vascular endothelial cells have use FcRn. In review, we summarize what known about function kidney. We discuss how therapeutic benefits, newer inhibiting are being treat Lastly, will which diseases may respond inhibitors further work studying lead therapies now not only be needed transfer across but essential or transcytosis monomeric cells. Thus, molecule responsible long half-lives these serum proteins. required trafficking immune complexes (ICs) lysosome proteolytic degradation ICs presentation on major histocompatibility complex II (MHCII), thereby playing key role adaptive immunity. multifaceted functions create therapeutics circulating antibodies play pathogenic role. describe structure focus receptor's modulation with potential existence first proposed Brambell1Brambell F.W. transmission from mother young catabolism immunoglobulins.Lancet. 1966; 2: 1087-1093Abstract PubMed Google Scholar 1966 between fetus. actual eventually purified rat's intestine Simister Mostov2Simister N.E. Mostov K.E. An Fc structurally related MHC I antigens.Nature. 1989; 337: 184-187Crossref Scopus (638) 1989. human heavy chain gene (Fcγ transporter gene, FCGRT) located chromosome 19. original sequencing FCGRT contained 7 exons 6 introns, 2 5 encoding signal sequence extracellular α1-α2-α3 domains, exon transmembrane domain, cytoplasmic tail.3Mikulska J.E. Pablo L. Canel J. Cloning analysis receptor.Eur J Immunogenet. 2000; 27: 231-240Crossref (32) Subsequent data Human Genome Project contain 10 instead originally proposed.4International Sequencing ConsortiumFinishing euchromatic genome.Nature. 2004; 431: 931-945Crossref (3689) orthologues most species interspecies conservation at amino acid level. chain, significant homology molecules, associates noncovalently ß2-microglobulin form heterodimer.2Simister Unlike molecule, peptide binding groove protein occluded thus unable present antigen.5Burmeister W.P. Gastinel L.N. et al.Crystal 2.2 A resolution MHC-related receptor.Nature. 1994; 372: 336-343Crossref (287) Scholar,6Raghavan M. Bjorkman P.J. shows pH-dependent stability differences correlating immunoglobulin release.Biochemistry. 1993; 32: 8654-8660Crossref (91) tail contains several conserved sorting motifs correct receptor.7Wu Z. Tryptophan- dileucine-based endocytosis signals receptor.J Biol Chem. 2001; 276: 5240-5247Abstract Full Text PDF (70) dileucine (L322/L323) tryptophan motif (W311) shown FcRn,7Wu experiments line does endogenously Another calmodulin-binding domain. Mutation residues domain decreased half-life Madin-Darby canine lacks endogenous expression, suggesting possible calcium/calmodulin regulation trafficking. Although other Fcγ receptors genetic variability, monomorphic, variability arising variable number tandem repeat (VNTR) polymorphisms labeled VNTR1 VNTR5 expression mRNA levels.8Gouilleux-Gruart V. Chapel H. Chevret S. al.Efficiency G replacement therapy common immunodeficiency: correlations clinical phenotype polymorphism receptor.Clin Exp Immunol. 2013; 171: 186-194Crossref (52) Scholar,9Sachs U.J. Socher I. Braeunlich C.G. al.A repeats influences transcriptional activity alpha-chain promoter.Immunology. 2006; 119: 83-89Crossref (86) More recently, additional VNTRs, designated VNTR6 VNTR8, subset patients ovarian cancer.10O'Shannessy D.J. Bendas K. Schweizer C. al.Correlation genomic immunoglobulin, farletuzumab pharmacokinetics relapsed cancer.Genomics. 2017; 109: 251-257Crossref (10) Despite name, expressed epithelial, endothelial, keratinocytes, hepatocytes. It organs kidney, intestinal tract, placenta, liver, hematopoietic system.11Pyzik Kozicky L.K. Gandhi A.K. Blumberg R.S. age receptor.Nat Rev 2023; 23: 415-432Crossref (16) predominantly intracellularly can surface, particularly antigen-presenting such monocytes dendritic cells.12Gan Ram Ober R.J. Ward E.S. Using multifocal plane microscopy reveal novel processes pathway.J Cell Sci. 126: 1176-1188Crossref (36) Scholar,13Rath T. Kuo T.T. Baker al.The immunologic IgG.J Clin 33: S9-S17Crossref (113) Within macrophages, monocytes, tubular (PCT), peritubular capillary glomerular podocytes (Figure 1).14Akilesh Huber T.B. Wu al.Podocytes clear basement membrane.Proc Natl Acad Sci U S A. 2008; 105: 967-972Crossref (223) Scholar, 15Haymann J.-P. Levraud Bouet al.Characterization localization adult kidney.J Am Soc Nephrol. 11: 632-639Crossref 16Sarav Wang Y. Hack B.K. al.Renal reclaims facilitates elimination 2009; 20: 1941-1952Crossref (112) 17Kidney Precision Medicine (KPMP)KPMP datasets "an atlas healthy injured states niches kidney".2022Google 18Kobayashi N. Suzuki Tsuge al.FcRn-mediated renal cells.Am Physiol Renal Physiol. 2002; 282: F358-F365Crossref (109) Whole tissue single-cell RNA samples chronic increasing expressing FcRn.17Kidney Interestingly, acute injury, descending thin limb phagocytes noted individuals.17Kidney Of note, no expressions reported data.17Kidney However, sources podocytes.14Akilesh Scholar,15Haymann Scholar,19Dylewski Dobrinskikh E. Lewis al.Differential facilitated vitro vivo.PLoS One. 2019; 14e0209732Crossref (15) Scholar,20Ichinose Ushigusa Nishino al.Lupus nephritis induction calcium/calmodulin-dependent kinase IV alteration their function.Arthritis Rheumatol. 2016; 68: 944-952Crossref (46) Similarly, PCT FcRn,15Haymann Scholar,16Sarav Scholar,18Kobayashi whereas demonstrated low expression.17Kidney Scholar,21Wu Uchimura Donnelly E.L. al.Comparative refinement PSC-derived organoid differentiation transcriptomics.Cell Stem Cell. 2018; 869-881.e868Abstract (343) These discrepancies resulted some controversy whether extent types reflect inherent limitations difficulty using methods, quantitative Initially, primary believed fetus well diversion degradative pathway toward transcytotic pathway. This diverting accounted proteins compared plays an presentation, indicating system. Below, general mechanisms handling albumin, IgG, then specifically binds portion acidic pH (5.0–6.5) rare exceptions (mouse IgG2b IgG3 allotypes) bind neutral pH.22Raghavan Bonagura V.R. Morrison S.L. Analysis dependence receptor/immunoglobulin interaction antibody variants.Biochemistry. 1995; 34: 14649-14657Crossref (283) Scholar,23Rodewald R. immunoglobulins rat.J Biol. 1976; 71: 666-669Crossref (218) At approximately 6, become protonated, allowing Glu115 Asp130 FcRn.24Medesan Matesoi D. Radu al.Delineation involved mouse IgG1.J 1997; 158: 2211-2217Crossref 25Martin W.L. West Jr., A.P. Gan Crystal 2.8 FcRn/heterodimeric complex: mechanism binding.Mol 7: 867-877Abstract (338) 26Kim J.K. Tsen M.F. Ghetie Identifying influence plasma clearance murine IgG1 fragments site-directed mutagenesis.Eur 24: 542-548Crossref (122) As level rises, protonation lost, leading disassociation IgG. allows late endosome/early FcRn/IgG 2). results back plasma, polarized beds basal apical membrane vice versa.27Ward Zhou Evidence support cellular homeostasis humans.Int 2003; 15: 187-195Crossref (170) Scholar,28Dickinson B.L. Badizadegan al.Bidirectional FcRn-dependent transport line.J Invest. 1999; 104: 903-911Crossref (370) requires presence motor myosin Vb, small GTPase Rab25, calcium-dependent calmodulin.29Tzaban Massol R.H. Yen pathways distinct display polarity.J 185: 673-684Crossref (145) Scholar,30Dickinson Claypool S.M. D'Angelo J.A. al.Ca2+-dependent calmodulin affects pathway.Mol 19: 414-423Crossref saturable; consequently, when exceed capability FcRn, excess trafficked degradation.27Ward X-ray crystallography revealed 2:1 stoichiometry. Recent arms able although precise details interactions remain elusive.31Schoch Kettenberger Mundigl O. al.Charge-mediated pharmacokinetics.Proc 2015; 112: 5997-6002Crossref (141) Scholar,32Wang W. Lu P. Fang al.Monoclonal identical sequences differentially pharmacokinetic consequences.Drug Metab Dispos. 2011; 39: 1469-1477Crossref (143) FcRn's studied vivo, knockout (KO) mice. Global KO mice significantly wild-type (approximately 0.5 mg/ml 1.5 wild-type), decrement IgA IgM levels.33Roopenian D.C. Christianson G.J. Sproule T.J. I-like controls perinatal transport, homeostasis, fate IgG-Fc-coupled drugs.J 170: 3528-3533Crossref (380) reduced 9 days 1.4 global KOs. Additional studies bone marrow chimera showed 5.2 animals 1.3 KOs marrow. had extended 2.3 days.34Akilesh Roopenian Shaw A.S. Neonatal FcR marrow-derived protect catabolism.J 2007; 179: 4580-4588Crossref (222) Further conditional deletion both (8.2 hours vs. 217.8 hours, respectively), affected.35Montoyo H.P. Vaccaro Hafner al.Conditional I-related reveals sites mice.Proc 106: 2788-2793Crossref (169) Serum almost 4-fold lower, 2-fold lower wild-type.35Montoyo indicate reclamation There documented cases deficiency humans. directly affect familial hypercatabolic hypoproteinemia, mutation prevents resulting hypoalbuminemia, levels, severely proteins.36Waldmann T.A. Terry W.D. Familial hypoproteinemia. disorder immunoglobulin.J 1990; 86: 2093-2098Crossref (85) Cultured lines determine compartments occurs. Early appeared early endosomes (EEA1 Rab5+ compartments) (Rab4 Rab11a+ spatial imaging optimal.37Ober Martinez Lai X. al.Exocytosis mediated receptor, FcRn: single-molecule level.Proc 101: 11076-11081Crossref (225) 38Ward al.From exocytosis: association Rab4 Rab11 GTPases during recycling.Mol 2005; 16: 2028-2038Crossref (158) 39Ober al.Visualizing site dynamics salvage FcRn1.J 172: 2021-2029Crossref (261) thought enter via pinocytosis (EEA1-, Rab5-, Rab4-, Rab11a-positive 6. Subsequently, separates Rab4+ endosomes. Ultimately, bounds delivered where fusion vesicles release cell.37Ober Albumin, 21 28 days, highest concentration humans.40Chaudhury Mehnaz Robinson J.M. complex-related prolongs lifespan.J Med. 197: 315-322Crossref (488) Albumin carrier ions compounds fatty acids bilirubin regulating oncotic pressure. diverts pathway, 2).35Montoyo Scholar,40Chaudhury 1:1 ratio, 200-fold lower) pH.41Chaudhury Brooks C.L. Carter al.Albumin FcRn-IgG interaction.Biochemistry. 45: 4983-4990Crossref (233) separate thus, same time.41Chaudhury Studies after uptake, endosomal compartments, engineered impaired preferentially directed lysosome. increased affinity recycled appears culture media.38Ward Scholar,42Schmidt E.G.W. Hvam M.L. Antunes F. al.Direct demonstration (FcRn)-driven albumin.J 292: 13312-13322Abstract sorts differently. above, salvaged lysosomal transcytosed. contrast, 3).43Weflen A.W. Baier Tang Q.J. al.Multivalent divert lysosomes exclusion tubules.Mol 2398-2405Crossref (71) differential result FcRn-ICs due size complexes. FcRn-mediated digestion molecules. seminal study Qiao al.44Qiao S.W. Kobayashi Johansen F.E. al.Dependence antibody-mediated FcRn.Proc 9337-9342Crossref (213) definitively IC increases efficiency CD4+ T efficient cross-presentation CD8−CD11b+ CD8+CD11b− CD8+ cells.45Baker al.Neonatal regulates CD8-CD11b+ cells.Proc 108: 9927-9932Crossref requirement subsets likely fact endocytic pH, diminishes Direct evidence importance comes rodent studies, showing confers protection Citrobacter rodentium infectious colitis model T-cell activation pathogen,46Yoshida mucosal responses luminal bacteria.J 116: 2142-2151Crossref (196) mouse, Clostridiodes difficile infection Lyme models.47Amadou Amani Lang G.A. Ballard J.D. immunization-induced difficile-specific gut against susceptibility.Infect Immun. 2021; 89e0027421Crossref (3) Scholar,48Crowley Alroy ameliorates arthritis.Int 18: 409-414Crossref (5) examined PCT. mice, Akilesh al.14Akilesh lack leads accumulation glomerulus, readily apparent months age. accumulated primarily mesangium deposition seen wild type. Podocyte-specific mesangial age, worsening expansion age.19Dylewski Consistent cultured

Language: Английский

The immunoregulatory roles of non-haematopoietic cells in the kidney DOI
George C. Tsokos,

Afroditi Boulougoura,

Vivek Kasinath

et al.

Nature Reviews Nephrology, Journal Year: 2023, Volume and Issue: 20(4), P. 206 - 217

Published: Nov. 20, 2023

Language: Английский

Citations

12
Exploiting the neonatal crystallizable fragment receptor to treat kidney disease DOI Creative Commons
James Dylewski, George Haddad, Judith Blaine

et al.

Kidney International, Journal Year: 2023, Volume and Issue: 105(1), P. 54 - 64

Published: Oct. 29, 2023

The neonatal crystallizable fragment receptor (FcRn) was initially discovered as the that allowed passive immunity in newborns by transporting maternal IgG through placenta and enterocytes. Since its initial discovery, FcRn has been found to exist throughout all stages of life many different cell types. Beyond immunity, is necessary for intrinsic albumin recycling important antigen processing presentation. Given multiple roles, used disease treatments including a new class agents were developed inhibit treatment variety autoimmune diseases. Certain populations within kidney also express high levels this receptor. Specifically, podocytes, proximal tubule epithelial cells, vascular endothelial cells have use FcRn. In review, we summarize what known about function kidney. We discuss how therapeutic benefits, newer inhibiting are being treat Lastly, will which diseases may respond inhibitors further work studying lead therapies now not only be needed transfer across but essential or transcytosis monomeric cells. Thus, molecule responsible long half-lives these serum proteins. required trafficking immune complexes (ICs) lysosome proteolytic degradation ICs presentation on major histocompatibility complex II (MHCII), thereby playing key role adaptive immunity. multifaceted functions create therapeutics circulating antibodies play pathogenic role. describe structure focus receptor's modulation with potential existence first proposed Brambell1Brambell F.W. transmission from mother young catabolism immunoglobulins.Lancet. 1966; 2: 1087-1093Abstract PubMed Google Scholar 1966 between fetus. actual eventually purified rat's intestine Simister Mostov2Simister N.E. Mostov K.E. An Fc structurally related MHC I antigens.Nature. 1989; 337: 184-187Crossref Scopus (638) 1989. human heavy chain gene (Fcγ transporter gene, FCGRT) located chromosome 19. original sequencing FCGRT contained 7 exons 6 introns, 2 5 encoding signal sequence extracellular α1-α2-α3 domains, exon transmembrane domain, cytoplasmic tail.3Mikulska J.E. Pablo L. Canel J. Cloning analysis receptor.Eur J Immunogenet. 2000; 27: 231-240Crossref (32) Subsequent data Human Genome Project contain 10 instead originally proposed.4International Sequencing ConsortiumFinishing euchromatic genome.Nature. 2004; 431: 931-945Crossref (3689) orthologues most species interspecies conservation at amino acid level. chain, significant homology molecules, associates noncovalently ß2-microglobulin form heterodimer.2Simister Unlike molecule, peptide binding groove protein occluded thus unable present antigen.5Burmeister W.P. Gastinel L.N. et al.Crystal 2.2 A resolution MHC-related receptor.Nature. 1994; 372: 336-343Crossref (287) Scholar,6Raghavan M. Bjorkman P.J. shows pH-dependent stability differences correlating immunoglobulin release.Biochemistry. 1993; 32: 8654-8660Crossref (91) tail contains several conserved sorting motifs correct receptor.7Wu Z. Tryptophan- dileucine-based endocytosis signals receptor.J Biol Chem. 2001; 276: 5240-5247Abstract Full Text PDF (70) dileucine (L322/L323) tryptophan motif (W311) shown FcRn,7Wu experiments line does endogenously Another calmodulin-binding domain. Mutation residues domain decreased half-life Madin-Darby canine lacks endogenous expression, suggesting possible calcium/calmodulin regulation trafficking. Although other Fcγ receptors genetic variability, monomorphic, variability arising variable number tandem repeat (VNTR) polymorphisms labeled VNTR1 VNTR5 expression mRNA levels.8Gouilleux-Gruart V. Chapel H. Chevret S. al.Efficiency G replacement therapy common immunodeficiency: correlations clinical phenotype polymorphism receptor.Clin Exp Immunol. 2013; 171: 186-194Crossref (52) Scholar,9Sachs U.J. Socher I. Braeunlich C.G. al.A repeats influences transcriptional activity alpha-chain promoter.Immunology. 2006; 119: 83-89Crossref (86) More recently, additional VNTRs, designated VNTR6 VNTR8, subset patients ovarian cancer.10O'Shannessy D.J. Bendas K. Schweizer C. al.Correlation genomic immunoglobulin, farletuzumab pharmacokinetics relapsed cancer.Genomics. 2017; 109: 251-257Crossref (10) Despite name, expressed epithelial, endothelial, keratinocytes, hepatocytes. It organs kidney, intestinal tract, placenta, liver, hematopoietic system.11Pyzik Kozicky L.K. Gandhi A.K. Blumberg R.S. age receptor.Nat Rev 2023; 23: 415-432Crossref (16) predominantly intracellularly can surface, particularly antigen-presenting such monocytes dendritic cells.12Gan Ram Ober R.J. Ward E.S. Using multifocal plane microscopy reveal novel processes pathway.J Cell Sci. 126: 1176-1188Crossref (36) Scholar,13Rath T. Kuo T.T. Baker al.The immunologic IgG.J Clin 33: S9-S17Crossref (113) Within macrophages, monocytes, tubular (PCT), peritubular capillary glomerular podocytes (Figure 1).14Akilesh Huber T.B. Wu al.Podocytes clear basement membrane.Proc Natl Acad Sci U S A. 2008; 105: 967-972Crossref (223) Scholar, 15Haymann J.-P. Levraud Bouet al.Characterization localization adult kidney.J Am Soc Nephrol. 11: 632-639Crossref 16Sarav Wang Y. Hack B.K. al.Renal reclaims facilitates elimination 2009; 20: 1941-1952Crossref (112) 17Kidney Precision Medicine (KPMP)KPMP datasets "an atlas healthy injured states niches kidney".2022Google 18Kobayashi N. Suzuki Tsuge al.FcRn-mediated renal cells.Am Physiol Renal Physiol. 2002; 282: F358-F365Crossref (109) Whole tissue single-cell RNA samples chronic increasing expressing FcRn.17Kidney Interestingly, acute injury, descending thin limb phagocytes noted individuals.17Kidney Of note, no expressions reported data.17Kidney However, sources podocytes.14Akilesh Scholar,15Haymann Scholar,19Dylewski Dobrinskikh E. Lewis al.Differential facilitated vitro vivo.PLoS One. 2019; 14e0209732Crossref (15) Scholar,20Ichinose Ushigusa Nishino al.Lupus nephritis induction calcium/calmodulin-dependent kinase IV alteration their function.Arthritis Rheumatol. 2016; 68: 944-952Crossref (46) Similarly, PCT FcRn,15Haymann Scholar,16Sarav Scholar,18Kobayashi whereas demonstrated low expression.17Kidney Scholar,21Wu Uchimura Donnelly E.L. al.Comparative refinement PSC-derived organoid differentiation transcriptomics.Cell Stem Cell. 2018; 869-881.e868Abstract (343) These discrepancies resulted some controversy whether extent types reflect inherent limitations difficulty using methods, quantitative Initially, primary believed fetus well diversion degradative pathway toward transcytotic pathway. This diverting accounted proteins compared plays an presentation, indicating system. Below, general mechanisms handling albumin, IgG, then specifically binds portion acidic pH (5.0–6.5) rare exceptions (mouse IgG2b IgG3 allotypes) bind neutral pH.22Raghavan Bonagura V.R. Morrison S.L. Analysis dependence receptor/immunoglobulin interaction antibody variants.Biochemistry. 1995; 34: 14649-14657Crossref (283) Scholar,23Rodewald R. immunoglobulins rat.J Biol. 1976; 71: 666-669Crossref (218) At approximately 6, become protonated, allowing Glu115 Asp130 FcRn.24Medesan Matesoi D. Radu al.Delineation involved mouse IgG1.J 1997; 158: 2211-2217Crossref 25Martin W.L. West Jr., A.P. Gan Crystal 2.8 FcRn/heterodimeric complex: mechanism binding.Mol 7: 867-877Abstract (338) 26Kim J.K. Tsen M.F. Ghetie Identifying influence plasma clearance murine IgG1 fragments site-directed mutagenesis.Eur 24: 542-548Crossref (122) As level rises, protonation lost, leading disassociation IgG. allows late endosome/early FcRn/IgG 2). results back plasma, polarized beds basal apical membrane vice versa.27Ward Zhou Evidence support cellular homeostasis humans.Int 2003; 15: 187-195Crossref (170) Scholar,28Dickinson B.L. Badizadegan al.Bidirectional FcRn-dependent transport line.J Invest. 1999; 104: 903-911Crossref (370) requires presence motor myosin Vb, small GTPase Rab25, calcium-dependent calmodulin.29Tzaban Massol R.H. Yen pathways distinct display polarity.J 185: 673-684Crossref (145) Scholar,30Dickinson Claypool S.M. D'Angelo J.A. al.Ca2+-dependent calmodulin affects pathway.Mol 19: 414-423Crossref saturable; consequently, when exceed capability FcRn, excess trafficked degradation.27Ward X-ray crystallography revealed 2:1 stoichiometry. Recent arms able although precise details interactions remain elusive.31Schoch Kettenberger Mundigl O. al.Charge-mediated pharmacokinetics.Proc 2015; 112: 5997-6002Crossref (141) Scholar,32Wang W. Lu P. Fang al.Monoclonal identical sequences differentially pharmacokinetic consequences.Drug Metab Dispos. 2011; 39: 1469-1477Crossref (143) FcRn's studied vivo, knockout (KO) mice. Global KO mice significantly wild-type (approximately 0.5 mg/ml 1.5 wild-type), decrement IgA IgM levels.33Roopenian D.C. Christianson G.J. Sproule T.J. I-like controls perinatal transport, homeostasis, fate IgG-Fc-coupled drugs.J 170: 3528-3533Crossref (380) reduced 9 days 1.4 global KOs. Additional studies bone marrow chimera showed 5.2 animals 1.3 KOs marrow. had extended 2.3 days.34Akilesh Roopenian Shaw A.S. Neonatal FcR marrow-derived protect catabolism.J 2007; 179: 4580-4588Crossref (222) Further conditional deletion both (8.2 hours vs. 217.8 hours, respectively), affected.35Montoyo H.P. Vaccaro Hafner al.Conditional I-related reveals sites mice.Proc 106: 2788-2793Crossref (169) Serum almost 4-fold lower, 2-fold lower wild-type.35Montoyo indicate reclamation There documented cases deficiency humans. directly affect familial hypercatabolic hypoproteinemia, mutation prevents resulting hypoalbuminemia, levels, severely proteins.36Waldmann T.A. Terry W.D. Familial hypoproteinemia. disorder immunoglobulin.J 1990; 86: 2093-2098Crossref (85) Cultured lines determine compartments occurs. Early appeared early endosomes (EEA1 Rab5+ compartments) (Rab4 Rab11a+ spatial imaging optimal.37Ober Martinez Lai X. al.Exocytosis mediated receptor, FcRn: single-molecule level.Proc 101: 11076-11081Crossref (225) 38Ward al.From exocytosis: association Rab4 Rab11 GTPases during recycling.Mol 2005; 16: 2028-2038Crossref (158) 39Ober al.Visualizing site dynamics salvage FcRn1.J 172: 2021-2029Crossref (261) thought enter via pinocytosis (EEA1-, Rab5-, Rab4-, Rab11a-positive 6. Subsequently, separates Rab4+ endosomes. Ultimately, bounds delivered where fusion vesicles release cell.37Ober Albumin, 21 28 days, highest concentration humans.40Chaudhury Mehnaz Robinson J.M. complex-related prolongs lifespan.J Med. 197: 315-322Crossref (488) Albumin carrier ions compounds fatty acids bilirubin regulating oncotic pressure. diverts pathway, 2).35Montoyo Scholar,40Chaudhury 1:1 ratio, 200-fold lower) pH.41Chaudhury Brooks C.L. Carter al.Albumin FcRn-IgG interaction.Biochemistry. 45: 4983-4990Crossref (233) separate thus, same time.41Chaudhury Studies after uptake, endosomal compartments, engineered impaired preferentially directed lysosome. increased affinity recycled appears culture media.38Ward Scholar,42Schmidt E.G.W. Hvam M.L. Antunes F. al.Direct demonstration (FcRn)-driven albumin.J 292: 13312-13322Abstract sorts differently. above, salvaged lysosomal transcytosed. contrast, 3).43Weflen A.W. Baier Tang Q.J. al.Multivalent divert lysosomes exclusion tubules.Mol 2398-2405Crossref (71) differential result FcRn-ICs due size complexes. FcRn-mediated digestion molecules. seminal study Qiao al.44Qiao S.W. Kobayashi Johansen F.E. al.Dependence antibody-mediated FcRn.Proc 9337-9342Crossref (213) definitively IC increases efficiency CD4+ T efficient cross-presentation CD8−CD11b+ CD8+CD11b− CD8+ cells.45Baker al.Neonatal regulates CD8-CD11b+ cells.Proc 108: 9927-9932Crossref requirement subsets likely fact endocytic pH, diminishes Direct evidence importance comes rodent studies, showing confers protection Citrobacter rodentium infectious colitis model T-cell activation pathogen,46Yoshida mucosal responses luminal bacteria.J 116: 2142-2151Crossref (196) mouse, Clostridiodes difficile infection Lyme models.47Amadou Amani Lang G.A. Ballard J.D. immunization-induced difficile-specific gut against susceptibility.Infect Immun. 2021; 89e0027421Crossref (3) Scholar,48Crowley Alroy ameliorates arthritis.Int 18: 409-414Crossref (5) examined PCT. mice, Akilesh al.14Akilesh lack leads accumulation glomerulus, readily apparent months age. accumulated primarily mesangium deposition seen wild type. Podocyte-specific mesangial age, worsening expansion age.19Dylewski Consistent cultured

Language: Английский

Citations

3