ライフサイエンスコーパス: pIgR

1 pIgR actively transports dIgA from the circulation acros

2 pIgR down-regulation in COPD correlates with disease sev

3 pIgR downregulation was selectively observed in patients

4 pIgR expression is reduced in chronic obstructive pulmon

5 pIgR expression is, in part, driven by aberrant STAT6 pa

6 pIgR expression was decreased in the ethmoidal mucosa in

7 pIgR immunostaining in the bronchial epithelium is decre

8 pIgR mRNA and protein also decline in P(+) E. coli-infec

9 pIgR(-/-) and pIgR(+/+) mice had comparable levels of in

10 IL-4, pIgR, IgA, and phosphorylated JAK-1 were significantly i

11 is-selected peptides map to the same 402-410 pIgR-binding Calpha3 site.

12 of receptor oligomerization, we show that a pIgR:zeta chimeric receptor expressed in Jurkat cells in

13 We propose that it may be possible to use a pIgR binding motif to deliver antigen-specific dIgA and

14 de detailed models for SC structure, address pIgR evolution, and demonstrate that SC uses multiple co

15 All pIgR binding IgA sequences contain a conserved three ami

16 We now report that levels of IRF-1 and pIgR mRNA are coordinately regulated in HT-29 cells by T

17 ggest targeting the dysbiotic microbiome and pIgR-mediated sIgA transport as potential therapeutic ap

18 acterial numbers significantly in normal and pIgR-deficient mice, and depletion of IgG abrogated this

19 pIgR(-/-) and pIgR(+/+) mice had comparable levels of inflammation, de

20 ysaccharide Ab locally and systemically, and pIgR(-/-) mice produced levels of total serum Ab after v

21 omes and subsequently intersects the TfR and pIgR pathways at a perinuclear Rab11-negative compartmen

22 ction, because both vaccinated wild-type and pIgR(-/-) mice were fully protected from lethal systemic

23 Serum anti-pIgR autoantibody levels were significantly increased in

24 (+)ACE2(+) cholangiocytes and targeting anti-pIgR autoantibodies may be valuable strategies for thera

25 he Th2 cytokines, IL-4 and IL-13, as well as pIgR, and luminal IgA compared with chow.

26 to both solubilized and membrane-associated pIgR, suggesting that binding can occur while the pIgR i

27 further investigated the interaction between pIgR and CaM using Madin-Darby canine kidney cells stabl

28 nd of the resulting immune complexes to bind pIgR.

29 fork' structure that is involved in binding pIgR.

30 ion of pIgR transcytosis and/or signaling by pIgR.

31 ess IgA dependent in mice, was unaffected by pIgR deficiency, indicating that pIgR had no physiologic

32 Inasmuch as this mouse B cell pIgR binds IgM better than IgA, it is similar to human p

33 -B, preventing expression of epithelial cell pIgR and decreasing sIgA.

34 y identical with that of the epithelial cell pIgR throughout its external, transmembrane, and intracy

35 from rat, mouse, and rabbit epithelial cell pIgRs that bind IgA but not IgM.

36 In contrast, pIgR transcription was up-regulated in smokers with or w

37 In contrast, pIgR(-/-) mice, which lack the receptor to transcytose p

38 In ALI (vs. submerged) cultures, pIgR expression was strongly induced, whereas pIgR expre

39 It is proposed that P fimbriae decrease pIgR expression in the kidney and consequently decrease

40 SPD-MAA decreased pIgR in HBECs.

41 lammatory bowel diseases, in which decreased pIgR is seen in concert with a dysregulated microbiota.

42 Polymeric IgR-deficient (pIgR(-/-)) mice, which lack the receptor that transports

43 polymeric immunoglobulin receptor-deficient (pIgR(-/-)) mice, which lack SIgA, spontaneously develop

44 The mean amplitude of 23 different pIgR peptides correlated negatively with the estimated g

45 ich in turn stimulates the transport of dIgA-pIgR complex from a postmicrotubule compartment to the a

46 P(+)-infected mice downregulate pIgR mRNA and protein levels compared with P(-)-infected

47 structure of teleost fish SC (tSC), an early pIgR ancestor.

48 This enables pIgR molecules that have bound dIgA at the basolateral s

49 up-regulate transcription of genes encoding pIgR and a number of proinflammatory factors, but the ef

50 Expression of mRNA encoding pIgR and several proinflammatory genes increased acutely

51 Epithelial pIgR expression is decreased in patients with CRSwNP and

52 ine whether P(+) E. coli regulate epithelial pIgR expression and IgA transport into the urine.

53 African green monkey kidney cells expressing pIgR demonstrated HIV excretion that was dependent on th

54 Darby Canine Kidney transcytosis assay, for pIgR-mediated transport through epithelial cells.

55 gA oligomerization and imparts asymmetry for pIgR binding and transcytosis.

56 patients retains its aberrant imprinting for pIgR expression.

57 Selection of random peptides for pIgR binding and comparison with the IgA sequence sugges

58 e lacking the J chain, which is required for pIgR-dependent transepithelial IgA transport.

59 eries of patients (n = 116) were studied for pIgR expression and regulation.

60 Furthermore, pIgR is the most prominent 35S-labeled CaM-binding prote

61 Furthermore, pIgR peptides were significantly increased in cardiovasc

62 and provided a more detailed insight on how pIgR can be potentially cleaved to release the SC.

63 However, pIgR(-/-) mice had approximately 5-fold more systemic Ig

64 A missense mutation in human pIgR, A580V, is associated with IgA nephropathy and naso

65 Deletional analysis of human pIgR revealed that the lack of either D3 or D4 resulted

66 inding motif(s) in the D3/D4 region of human pIgR, which is functionally separated from the IgA-bindi

67 We report here that the human pIgR (hpIgR) can bind to a major pneumococcal adhesin, C

68 IgM better than IgA, it is similar to human pIgR and differs from rat, mouse, and rabbit epithelial

69 sting of 16HBEo cells transfected with human pIgR complementary DNA, which overexpress the receptor,

70 such as transferrin (TfR) and polymeric IgA (pIgR) receptors.

71 lular immune responses, characterized by IgA:pIgR interactions in tumor cells, determine the progress

72 The polymeric IgR (pIgR) mediates transcytosis of IgA across epithelial bar

73 a dominant role, was severely compromised in pIgR-deficient mice despite significant fecal IgA output

74 The decrease in pIgR was associated with decreased urinary IgA levels in

75 We propose that the defects in pIgR trafficking caused by the A580V mutation may underl

76 ive airway wall remodelling and emphysema in pIgR(-/-) mice are associated with an altered lung micro

77 IV replication, nor did D47A and D19A IgA in pIgR- cells, incapable of transcytosing IgA.

78 exposure to TNF caused a marked increase in pIgR mRNA stability and a small but significant decrease

79 this recruitment was a striking induction in pIgR expression by the bronchial epithelium and a subseq

80 e in dIgA assembly but a significant role in pIgR/SC binding to dIgA.

81 Several factors increase pIgR expression in human epithelial cells, including IL-

82 epithelial HT-29 cells with IL-17 increased pIgR expression.

83 inflammation were associated with increased pIgR and PAFr levels in the lungs and increased suscepti

84 a crucial role for this cytokine in inducing pIgR expression by the epithelium.

85 ogenous TGF-beta1 dose-dependently inhibited pIgR production, whereas pIgR increased on blockade of T

86 fic for a commensal Ag, increased intestinal pIgR and IgA.

87 The levels of intestinal pIgR and IgA in B6.IL-17R (IL-17R(-/-)) mice were lower

88 estinal homeostasis by regulating intestinal pIgR expression and IgA secretion.

89 Additionally, small intestinal pIgR was decreased ~50% in EdnrB(NCC-/-) mice.

90 Kidney pIgR and urine IgA levels were analyzed in a mouse model

91 been examined using polymeric IgR knockout (pIgR(-/-)) mice, which lack the ability to actively secr

92 ton X-114-solubilized, metabolically labeled pIgR-expressing Madin-Darby canine kidney cells.

93 basolateral membrane from CRE, Megalin, like pIgR, traffics to subapical Rab11-positive apical recycl

94 This study also links pIgR down-regulation to TGF-beta-driven reprogramming of

95 d from the published sequence of mouse liver pIgR indicate that T560 cells express mRNA virtually ide

96 required for their transport into the lumen, pIgR or J chain, cleared C. rodentium normally.

97 TNF production was insufficient to maintain pIgR and proinflammatory gene expression after withdrawa

98 s also demonstrated that avian and mammalian pIgR share related, but distinct, mechanisms of ligand b

99 Although several mammalian pIgR cDNAs, including mouse, have been cloned, genomic s

100 gA that increased caspase activation in MDCK-pIgR+ cells compared to serum-derived IgA from controls

101 t or fixed in 4% paraformaldehyde to measure pIgR expression via immunohistochemistry.

102 Tissue was homogenized to measure pIgR expression via Western blot or fixed in 4% paraform

103 Mechanistically, pIgR-dependent, antigen-independent IgA occupancy drove

104 immunoblots with specific rabbit anti-mouse pIgR.

105 In summary, we have isolated the murine pIgR gene and described its structure and organization.

106 isolation and characterization of the murine pIgR gene that spans 32 kb and contains 11 exons.

107 tably expressing cloned wild-type and mutant pIgR.

108 Wild-type, but not pIgR(-/-) mice were protected against infection with ser

109 ot the Tyr734), controls both the ability of pIgR to cause dIgA-induced tyrosine phosphorylation of t

110 t the basolateral surface and the ability of pIgR to dimerize.

111 rs or deletion of the last 30 amino acids of pIgR cytoplasmic tail prevents IgA-stimulated protein ty

112 Analysis of pIgR deletion mutants reveals that the same discrete por

113 our study was to evaluate the association of pIgR peptides with the cardio-renal syndrome in a large

114 Furthermore, CbpA binding of pIgR did not appear to require Ca2+ or Mg2+.

115 Re-derivation of pIgR(-/-) mice in germ-free conditions or treatment with

116 gnaling, Arg657 in the cytoplasmic domain of pIgR, and possibly GTP hydrolysis by rab3b.

117 thelial cells where the N-terminal domain of pIgR, termed secretory component (SC), is proteolyticall

118 tly interacts with the cytoplasmic domain of pIgR.

119 e, we demonstrate that in vivo expression of pIgR mRNA is greatly depressed in the intestine and live

120 ation moves across the cell independently of pIgR movement or microtubules and acts through the tyros

121 Our data suggest that inhibition of pIgR and PECAM-1 has the potential to prevent pneumococc

122 Individual mice with lower levels of pIgR and intestinal-secreted IgA correlated with increas

123 g pneumonia, aged mice had reduced levels of pIgR and PAFr and less NFkB activation, despite greater

124 ecrosis factor-alpha had increased levels of pIgR and PAFr in their lungs and were more susceptible t

125 Both dsRNA and LPS up-regulated levels of pIgR mRNA and cell surface pIgR protein.

126 nd IFN-gamma increase steady state levels of pIgR mRNA in both human intestinal (HT29) and airway (Ca

127 ependent increases in steady state levels of pIgR mRNA were inhibited by cycloheximide and by protein

128 IRF-1 only weakly correlated with levels of pIgR mRNA, suggesting that additional transcription fact

129 The extra-cellular portion of pIgR consists of five Ig-like domains (D1-D5), each of w

130 of pIgR and pIgA, and seemingly the rate of pIgR cleavage.

131 obulin receptor [pIgR]), apical recycling of pIgR-IgA, and accumulation of newly synthesized GP-135 a

132 This region of pIgR constitutes an autonomous basolateral targeting sig

133 st that CaM may be involved in regulation of pIgR transcytosis and/or signaling by pIgR.

134 Through the generation of a series of pIgR chimeric constructs, we have tested the ability of

135 ne IgA was greatly increased in the serum of pIgR-deficient mice, conferred passive protection agains

136 Synthesis of pIgR is up-regulated by the proinflammatory cytokines TN

137 hrough NF-kappaB to enhance transcription of pIgR mRNA.

138 g receptor (pIgR) stimulates transcytosis of pIgR across epithelial cells.

139 mutation reduces the rate of transcytosis of pIgR and pIgA, and seemingly the rate of pIgR cleavage.

140 with thapsigargin stimulates transcytosis of pIgR, while the intracellular Ca chelator BAPTA-AM inhib

141 d to achieve dIgA-stimulated transcytosis of pIgR.

142 These results, together with prior data on pIgR-mediated immune neutralization of luminal cholera t

143 ought to determine the CbpA-binding motif on pIgR by deletional analysis.

144 tein PspC binds, but to a lower extent, only pIgR.

145 to pIgR stimulates transcytosis of the pIgA-pIgR complex via a signal transduction pathway that is d

146 e against respiratory pathogens by promoting pIgR-mediated transport of secretory IgA and IgM into th

147 In contrast, rabbit pIgR (rpIgR) did not bind to CbpA and its expression in

148 he mouse polymeric immuno-globulin receptor (pIgR) is 654 nt long and, despite being surrounded by la

149 found that intestinal polymeric Ig receptor (pIgR) and IgA production was impaired in T cell-deficien

150 fected with the human polymeric Ig receptor (pIgR) and the cells studied by flow cytometric analysis

151 Polymeric Ig receptor (pIgR) is a central player in mucosal immunity that media

152 The polymeric Ig receptor (pIgR) is conserved in mammals and has an avian homologue

153 cates that the receptor is poly-Ig receptor (pIgR) known in humans and domestic cattle to bind both I

154 The polymeric Ig receptor (pIgR) mediates transport of IgA across mucosal epithelia

155 TGF-B) down-regulates polymeric Ig receptor (pIgR) on mucosal epithelium, resulting in decreased sIgA

156 which is bound by the polymeric Ig receptor (pIgR) on the basolateral surface of epithelial cells and

157 globulin (Ig)A to the polymeric Ig receptor (pIgR) stimulates transcytosis of pIgR across epithelial

158 The polymeric Ig receptor (pIgR) transcytoses its ligand, dimeric IgA (dIgA), from

159 The polymeric Ig receptor (pIgR) transports polymeric Abs across epithelia to the m

160 s, IgA, secreted IgM, polymeric Ig receptor (pIgR), or J chain.

161 The polymeric Ig receptor (pIgR), produced by renal epithelia, transports IgA into

162 fected to express the polymeric Ig receptor (pIgR), were transfected with HIV proviral DNA, and intra

163 ia is mediated by the polymeric Ig receptor (pIgR), which is expressed on the basolateral surface of

164 he apical surface via polymeric Ig receptor (pIgR)-mediated binding and the internalization of HIV-Ig

165 Polymeric Ig receptor (pIgR)-mediated IgA transport into the intestinal lumen w

166 s the hypothesis that polymeric Ig receptor (pIgR)-mediated secretory IgA immunity could be impaired

167 ns is mediated by the polymeric Ig receptor (pIgR).

168 d in the transcytotic polymeric Ig receptor (pIgR).

169 eric Igs (pIg) by the polymeric Ig receptor (pIgR).

170 nal secretions by the polymeric Ig receptor (pIgR).

171 the human polymeric immunoglobulin receptor (pIgR) and enhances pneumococcal adhesion to and invasion

172 ining the polymeric immunoglobulin receptor (pIgR) and located subjacent to the apical surface.

173 eceptors: polymeric immunoglobulin receptor (pIgR) and platelet endothelial cell adhesion molecule (P

174 proteins polymeric immunoglobulin receptor (pIgR) and platelet-activating factor receptor (PAFr) to

175 ssions of polymeric immunoglobulin receptor (pIgR) by tumor cells and its occupancy by IgA were super

176 ing human polymeric immunoglobulin receptor (pIgR) expressing Madine-Darby canine kidney (MDCK) cells

177 that the polymeric immunoglobulin receptor (pIgR) is highly expressed by renal cyst-lining cells.

178 The polymeric immunoglobulin receptor (pIgR) is important in host defense, transporting antibod

179 is of the polymeric immunoglobulin receptor (pIgR) is stimulated by binding of its ligand, dimeric Ig

180 ed by the polymeric immunoglobulin receptor (pIgR) on mucosal and glandular epithelial cells.

181 The polymeric immunoglobulin receptor (pIgR) plays a crucial role in mucosal immunity against m

182 The polymeric immunoglobulin receptor (pIgR) transcytoses dimeric IgA (dIgA) from the basolater

183 The polymeric immunoglobulin receptor (pIgR) transports immunoglobulins from the basolateral to

184 ense, the polymeric immunoglobulin receptor (pIgR) transports polymeric IgA and IgM across epithelia

185 ated that polymeric immunoglobulin receptor (pIgR) was highly expressed in DUOX2(+)ACE2(+) cholangioc

186 tein, the polymeric immunoglobulin receptor (pIgR), and a secretory protein, gp80, we show that pIgR

187 ct of the polymeric immunoglobulin receptor (pIgR), is added during the transit of dimeric IgA throug

188 protein, polymeric immunoglobulin receptor (pIgR), which is reduced during PN.

189 reported polymeric immunoglobulin receptor (pIgR)-binding site, which might explain why secretory Ig

190 receptor, polymeric immunoglobulin receptor (pIgR).

191 d via the polymeric immunoglobulin receptor (pIgR).

192 m via the polymeric immunoglobulin receptor (pIgR).

193 ed by the polymeric immunoglobulin receptor (pIgR).

194 ed by the polymeric immunoglobulin receptor (pIgR).

195 , via the polymeric immunoglobulin receptor (pIgR).

196 in is the polymeric immunoglobulin receptor (pIgR).

197 s, by the polymeric immunoglobulin receptor (pIgR).

198 (pIgA) is transcytosed by the pIgA receptor (pIgR) across mucosal epithelial cells.

199 The role of the polymeric receptor (pIgR) is to transport polymeric IgA across various mucos

200 d for the polymeric immunoglobulin receptor [pIgR]), apical recycling of pIgR-IgA, and accumulation o

201 that signaling through TLRs may up-regulate pIgR expression by intestinal epithelial cells and thus

202 ling through LPS/TLR4 appears to up-regulate pIgR expression while minimizing proinflammatory respons

203 s lung epithelial cell TGF-B, down-regulates pIgR, and decreases sIgA transcytosis.

204 , studies demonstrate that IL-4 up-regulates pIgR production via Janus kinase/signal transducers and

205 Consistent with our previous work, sIgA, pIgR, and IL-4 decreased with PN, whereas the addition o

206 We found that detergent-solubilized pIgR binds to CaM-agarose in a Ca(2+)-dependent fashion,

207 ion is necessary and sufficient to stimulate pIgR transcytosis.

208 binding to the pIgR control dIgA-stimulated pIgR transcytosis.

209 ring PN, we hypothesized that the suppressed pIgR is a result of decreased JAK-1 and STAT-6 phosphory

210 gulated levels of pIgR mRNA and cell surface pIgR protein.

211 ntrols, and assayed for IgA1/IgA2 synthesis, pIgR expression, production of secretory component (SC),

212 membrane, and delivery of newly synthesized pIgR from the Golgi to the basolateral membrane were all

213 nvolved in high-affinity binding to the T560 pIgR.

214 In this study, we demonstrate that pIgR can play a critical role in intestinal defense agai

215 this large cohort, we could demonstrate that pIgR is associated with the cardio-renal syndrome and pr

216 affected by pIgR deficiency, indicating that pIgR had no physiologic role when lower luminal IgA leve

217 and a secretory protein, gp80, we show that pIgR and gp80 protein synthesis and delivery are increas

218 These findings show that pIgR/SIgA deficiency in the airways leads to persistent

219 ation of luminal cholera toxin, suggest that pIgR is essential in intestinal defense against pathogen

220 Our results suggest that pIgR-mediated transcytosis of antagonistic antibodies in

221 These results suggest that pIgR-mediated transcytosis of pIgA-EBV through epitheliu

222 o-2-naphthalenesulfonamide), suggesting that pIgR binding to CaM is specific.

223 The pIgR's five Ig-like domains (D1-D5) undergo a conformati

224 Although the pIgR is constitutively transcytosed in the absence of li

225 eleasing SIgA, a complex of the dIgA and the pIgR ectodomain, called the secretory component (SC).

226 present, because recycling receptors and the pIgR were coisolated on the same elements.

227 suggest that ligand-induced signaling by the pIgR may regulate membrane traffic via well-known second

228 ions, but which were not transcytosed by the pIgR, did not inhibit intracellular HIV replication, nor

229 s that are both bound and transported by the pIgR, this study provides evidence that the pIgR-mediate

230 isotype-specific and was not mediated by the pIgR.

231 ss the epithelium, a process mediated by the pIgR.

232 main swap" mutants, the binding site for the pIgR on dimeric IgA (dIgA) was localized to the Calpha3

233 represented a potential binding site for the pIgR.

234 ting that an IgA receptor, distinct from the pIgR, asialoglycoprotein receptor, galactosyltransferase

235 associated with evolutionary changes in the pIgR protein.

236 These data localize the pIgR binding site on dimeric human IgA to this loop stru

237 mbrane-proximal 17-amino acid segment of the pIgR cytoplasmic tail.

238 Interestingly, the large fourth exon of the pIgR gene encodes two immunoglobulin-like extracellular

239 extracellular, ligand-binding portion of the pIgR is proteolytically cleaved.

240 secretory component (SC), the portion of the pIgR that remains bound to pig in secretions, and immuno

241 c physical and functional association of the pIgR with p62yes in rodent liver.

242 y which cytokines regulate expression of the pIgR, a central player in mucosal immunity.

243 component, the extracellular portion of the pIgR, linked to human alpha1-antitrypsin is effectively

244 nscriptional regulation of expression of the pIgR.

245 complex with the secretory component of the pIgR.

246 nding of dIgA stimulates transcytosis of the pIgR.

247 In addition, we replaced the pIgR's transmembrane domain with that of glycophorin A t

248 ing of dIgA to the pIgR, indicating that the pIgR can transduce a signal to the cytoplasmic machinery

249 pIgR, this study provides evidence that the pIgR-mediated mucosal secretion system may represent a m

250 ort of green fluorescent protein through the pIgR-specific cellular transcytosis system.

251 We report that dIgA binding to the pIgR causes activation of protein kinase C (PKC) and rel

252 that are activated upon dIgA binding to the pIgR control dIgA-stimulated pIgR transcytosis.

253 conclude that binding of dimeric IgA to the pIgR induces its dimerization and that this dimerization

254 e recently reported that dIgA binding to the pIgR induces translocation of protein kinase C, producti

255 second signal depends on dIgA binding to the pIgR solely at the basolateral surface and the ability o

256 osis is stimulated by binding of dIgA to the pIgR, indicating that the pIgR can transduce a signal to

257 , using a protein that binds directly to the pIgR, Streptococcus pneumoniae can co-opt the transcytos

258 ary epithelial cells of PBC patients via the pIgR and complex with PDC-E2, thereby potentially contri

259 suggesting that binding can occur while the pIgR is in intact membranes.

260 ciation of tyrosine kinase activity with the pIgR and in transcytosis of pIgA.

261 There, pIgR is proteolytically cleaved, releasing SIgA, a compl

262 This pIgR defect was associated with reduced levels of SC (P

263 ata suggest that during transcytosis through pIgR-positive cells, exposure to PDC-E2-specific dimeric

264 -1 and STAT-6, resulting in increased tissue pIgR and luminal IgA.

265 y an important role in bacterial adhesion to pIgR.

266 here to and invade human cells by binding to pIgR.

267 Binding of dIgA to pIgR at the basolateral surface stimulates subsequent tr

268 Binding of dIgA to pIgR causes a dissociation of the interaction with rab3b

269 n this area abrogated the binding of dIgA to pIgR, whereas adjacent substitutions in a beta-strand im

270 Binding of pIgA to pIgR stimulates transcytosis of the pIgA-pIgR complex vi

271 sity of recycling receptors and transcytotic pIgR in RRC membranes was similar to that in early endos

272 Finally, treating pIgR with a reducing agent abolished CbpA binding, sugge

273 owever, other biological functions for trout pIgR or trout secretory component (tSC) remain unknown.

274 Rainbow trout pIgR is known to transport IgT and IgM across epithelia.

275 However, binding of CaM to various pIgR mutants suggests that CaM binding is not necessary

276 gA-EBV complexes in the blood of mice, where pIgR-mediated transcytosis of IgA immune complexes throu

277 IgR expression was strongly induced, whereas pIgR expression and IgA-transcytosis capacity were decre

278 pendently inhibited pIgR production, whereas pIgR increased on blockade of TGF-beta1 activity during

279 canine kidney (MDCK) cells transfected with pIgR to determine the effect on viral antigen expression