ライフサイエンスコーパス: Siglec

1 ns with sialic acid-binding Ig-type lectins (siglecs).

2 taining the selectivity for hCD22 over other Siglecs.

3 of agents to cells expressing CD22 and other Siglecs.

4 s that express glycan ligands for the B cell Siglecs.

5 We also found that the expression of Siglec-1 (a member of sialic acid-binding Ig (I)-like le

6 0064), and marked by increased expression of SIGLEC-1 (CD169), a lectin-like receptor expressed on CD

7 Siglec-1 (sialoadhesin, CD169) is a surface receptor on

8 e functionally null or haploinsufficient for Siglec-1 activity in HIV-1 capture and trans-infection e

9 Mechanistically, Siglec-1 associates with adaptor protein DNAX-activation

10 ctious routes may compensate for the lack of Siglec-1 in fuelling HIV-1 dissemination within infected

11 s with the known in vitro functional role of Siglec-1 in HIV-1 trans-infection.

12 Knockdown of siglec-1 in RAW 264.7 cells resulted in inhibiting the p

13 Thus, Siglec-1 is a key receptor for macrophage/lymphocyte tra

14 lipid (GSL) GM3 on virus particles and CD169/Siglec-1 on MDCs.

15 Thus, Siglec-1 plays an important role in the development of e

16 However, Siglec-1 protein truncation does not have a measurable i

17 ndotoxin tolerant cells and the induction of Siglec-1 suppresses the innate immune response by promot

18 The enhanced TGF-beta1 production by Siglec-1 was significantly attenuated by spleen tyrosine

19 We determined that sialoadhesin (CD169; Siglec-1) is required for the capture of B cell-derived

20 CD169/Siglec-1, an I-type lectin that recognizes gangliosides,

21 particles, Gag, frequently co-localized with Siglec-1, and trans-infection, primarily of surface-boun

22 Here, we demonstrate that mouse Siglec-1, expressed on the surface of primary macrophage

23 isplayed strikingly different capacities for Siglec-1-mediated capture and trans-infection; N-butanoy

24 -dependent interaction of MLV particles with Siglec-1.

25 Siglec-1/CD169 is a myeloid-cell surface receptor critic

26 ialic acid is a critical determinant for the Siglec-1/MLV interaction.

27 promote an anti-inflammatory axis via glycan-Siglec-10 engagement.

28 Detection of Siglec-10 on intestinal CD11c(+) CD103(+) DCs added furt

29 In vitro infection of Siglec-10 overexpressing cells resulted in increased IL-

30 C. jejuni and purified flagellum to bind to Siglec-10, an immune-modulatory receptor.

31 munomodulatory Siglecs, such as Siglec-5 and Siglec-10.

32 acid capsule as a molecular mimic to engage Siglec-11 and escape killing.

33 Here, we studied the inhibitory receptor Siglec-11 that shows uniquely human expression in brain

34 Siglec-14 is absent from some humans because of a SIGLEC

35 flammatory signal, while stimulation through Siglec-14 is pro-inflammatory.

36 in-expressing GBS binds to both Siglec-5 and Siglec-14 on neutrophils and that the latter engagement

37 Siglec-5 and Siglec-14, expressed on monocytes and neutrophils, share

38 surfactant protein D, human galectin-8, and Siglec-14, to different NTHi clinical isolates.

39 ngly, neutrophils and monocytes also express Siglec-14, which has a ligand-binding domain almost iden

40 revealed Hsp70 as a ligand for Siglec-5 and Siglec-14.

41 of RANKL and supports further development of Siglec-15 antibodies as a novel class of bone loss thera

42 ion, lysosomal targeting, and degradation of Siglec-15 by inducing receptor dimerization.

43 At the molecular level, Siglec-15 interacts with the adapter protein DAP12 and c

44 In this report, we confirm that Siglec-15 is localized to the plasma membrane where it c

45 Previously, we identified Siglec-15, a little studied sialic acid-binding receptor

46 st, engagement of the activating counterpart Siglec-16 increases elimination of bacteria.

47 mouse Siglec-E with the activating module of Siglec-16.

48 The inhibitory functions of CD22/Siglec-2 and Siglec-G and their contributions to toleran

49 y comparative analysis of major CD33rSiglec (Siglec-3, Siglec-5, and Siglec-9) orthologs in humans, c

50 The immunomodulatory receptor Siglec-3/CD33 influences risk for late-onset Alzheimer's

51 TLR binders were human SIGLEC-5/9 and mouse Siglec-3/E/F.

52 for other immunomodulatory Siglecs, such as Siglec-5 and Siglec-10.

53 at beta-protein-expressing GBS binds to both Siglec-5 and Siglec-14 on neutrophils and that the latte

54 Siglec-5 and Siglec-14, expressed on monocytes and neutr

55 biased screen revealed Hsp70 as a ligand for Siglec-5 and Siglec-14.

56 a ligand-binding domain almost identical to Siglec-5 but signals via an activating motif, raising th

57 Hsp70 stimulation through Siglec-5 delivers an anti-inflammatory signal, while sti

58 c acid-binding immunoglobulin-like lectin 5 (Siglec-5), an inhibitory receptor on phagocytes.

59 ive analysis of major CD33rSiglec (Siglec-3, Siglec-5, and Siglec-9) orthologs in humans, chimpanzees

60 The promiscuous TLR binders were human SIGLEC-5/9 and mouse Siglec-3/E/F.

61 Further more, Siglec-6 was expressed at a higher level on a human pDC

62 these genes, we confirmed that expression of Siglec-6 was inhibited by E2-2.

63 Siglec 9 on neutrophils and Siglec 7 on NK cells are prominent examples of inhibitor

64 igand of sialic acid-binding Ig-like lectin (Siglec)-7, a siglec receptor expressed on DCs that media

65 The sialic acid-binding Ig-like lectins Siglec-7 and -9 are MHC class I-independent inhibitory r

66 Expression of Siglec-7 and -9 ligands was associated with susceptibili

67 imary tumor samples revealed that ligands of Siglec-7 and -9 were expressed on human cancer cells of

68 data suggest that the endocytic function of Siglec-7 can be exploited to deliver glycolipid Ags to t

69 An Ab to Siglec-7 completely blocked the binding of targeted lipo

70 , thereby recruiting the inhibitory receptor Siglec-7 expressed on the NK cell surface which subseque

71 Our data suggest that restoration of human Siglec-7 expression may be a novel therapeutic strategy

72 Over-expression of Siglec-7 in diabetic islets reduced cytokines, prevented

73 free lipid Ag or antigenic liposomes without Siglec-7 ligand.

74 d alphaMe Neu5Ac, the smallest known natural Siglec-7 ligand.

75 he first, high-affinity low molecular weight Siglec-7 ligands to interfere with cancer cell immune ev

76 gnant cells is to camouflage themselves with Siglec-7 ligands, thereby recruiting the inhibitory rece

77 Siglec-7 was expressed on beta-cells and down-regulated

78 ight against cancers, in particular blocking Siglec-7 with low molecular weight compounds.

79 es and bind with low micromolar Kd values to Siglec-7.

80 lic acid-binding immunoglobulin-like lectin (Siglec)-8 is a cell-surface protein expressed selectivel

81 Targeting saporin to Siglec-8 consistently caused extensive cell death in eos

82 and malignant mast cells by exploiting this Siglec-8 endocytic pathway.

83 Siglec-8 endocytosis required actin rearrangement, tyros

84 targeting of an agent to these cells through Siglec-8 endocytosis.

85 red to elicit the unanticipated finding that Siglec-8 engagement promotes rapid beta2-integrin-depend

86 he necessity of various proteins involved in Siglec-8 function for human eosinophils.

87 identify the signaling molecules involved in Siglec-8 function for human eosinophils.

88 These data demonstrate that Siglec-8 functions uniquely as an activating receptor on

89 etic sulfated sialoglycan ligand recognizing Siglec-8 in combination with integrin blocking antibodie

90 Siglec-8 intracellular trafficking was followed by confo

91 Siglec-8 is a CD33 subfamily cell-surface receptor selec

92 Siglec-8 is a human immune-inhibitory receptor that, whe

93 We sought to determine whether Siglec-8 is endocytosed in human eosinophils and maligna

94 idase treatment of eosinophils revealed that Siglec-8 is partially masked by sialylated cis ligands.

95 ligands and determined the structure of the Siglec-8 lectin domain in complex with its prime glycan

96 Internalized Siglec-8 localized to the lysosomal compartment.

97 After cytokine priming, Siglec-8 mAb or glycan ligand binding causes eosinophil

98 l ROS production and apoptosis suggests that Siglec-8 might instead function as an activating recepto

99 Finally, engagement of Siglec-8 on IL-5-primed eosinophils resulted in increase

100 structural and mechanistic insights into how Siglec-8 selectively recognizes its glycan target, ratio

101 Siglec-8 surface dynamics were examined by flow cytometr

102 requires an understanding of the dynamics of Siglec-8 surface expression.

103 as inhibitory receptors, but the ability of Siglec-8 to stimulate eosinophil ROS production and apop

104 ctroscopy to dissect the fine specificity of Siglec-8 toward different sialylated and sulfated carboh

105 Siglec-8 was also shuttled to the surface via a distinct

106 of the OSM(+) cells, 56% +/- 7% were CD16(+)Siglec-8(-), indicating neutrophil lineage.

107 ymal rEos found in nonasthmatic human lungs (Siglec-8+CD62L+IL-3Rlo cells) were phenotypically distin

108 he sputa of eosinophilic asthmatic patients (Siglec-8+CD62LloIL-3Rhi cells), suggesting that our find

109 monstrate whether a toxin can be targeted to Siglec-8-bearing cells to kill these cells.

110 bition of these kinases completely prevented Siglec-8-mediated eosinophil apoptosis.

111 a Rac GTPase inhibitor) completely inhibited Siglec-8-mediated eosinophil apoptosis.

112 Siglec-8-mediated ROS was generated through reduced nico

113 hibiting protein saporin was conjugated to a Siglec-8-specific antibody to examine the targeting of a

114 tion, and will enable the rational design of Siglec-8-targeted agonists to treat eosinophil- and mast

115 eral blood eosinophils, mast cell lines, and Siglec-8-transduced cells in the presence of inhibitors

116 Maximal endocytosis in Siglec-8-transduced HEK293T cells required an intact imm

117 Siglec 9 on neutrophils and Siglec 7 on NK cells are pro

118 nistic monoclonal antibodies to human Fas or Siglec-9 affected the viability of mouse neutrophils.

119 novel sialic acid-dependent ligand for human Siglec-9 and for other immunomodulatory Siglecs, such as

120 with this, a human polymorphism that reduced Siglec-9 binding to carcinomas was associated with impro

121 Here, we found that the presence of Siglec-9 defined a subset of cytotoxic NK cells with a m

122 Binding of MUC1-ST to Siglec-9 did not activate the phosphatases SHP-1 or SHP-

123 Blockade of Siglec-9 enhanced neutrophil activity against tumor cell

124 , and this effect was reversed by transgenic Siglec-9 expression in myelomonocytic cells.

125 Siglec-9 is a sialic-acid-binding lectin expressed predo

126 ere accompanied by a strong up-regulation of Siglec-9 ligands.

127 ll lung cancer patients, which suggests that Siglec-9 might be therapeutically targeted within the ri

128 have implications for the inhibitory role of siglec-9 on human neutrophils in sepsis and acute lung i

129 f major CD33rSiglec (Siglec-3, Siglec-5, and Siglec-9) orthologs in humans, chimpanzees, and baboons.

130 Interestingly, this Siglec-9+ NK cell population was reduced in the peripher

131 ecific MUC1 glycoform, through engagement of Siglec-9, 'educated' myeloid cells to release factors as

132 oprotein on erythrocytes, engaged neutrophil Siglec-9, a sialic acid-recognizing receptor known to da

133 Notably, Siglec-9, the functionally equivalent human paralog of S

134 e myelomonocytic lineage inhibitory receptor Siglec-9, thereby evading immunosurveillance.

135 Supporting this hypothesis, Siglec-9-expressing myelomonocytic cells found in human

136 ctivating pathway that follows engagement of Siglec-9.

137 iglec-E, the murine functional equivalent of Siglec-9.

138 trophils via agonistic antibodies to Fas and Siglec-9.

139 Primate Siglecs also show quantitative and qualitative intra- an

140 ity of a broad repression of TLR function by Siglecs and a sialidase-mediated de-repression that allo

141 iquely human interactions of a pathogen with Siglecs and support the long-standing hypothesis that ac

142 ic acid-binding immunoglobulin-like lectins (siglecs) and selectins, that are involved in multiple st

143 ted or self-associated signal through paired Siglecs, and may explain seemingly contradictory prior r

144 c acid-recognizing Ig superfamily lectins or Siglecs are a family of cell surface proteins largely ex

145 CD33-related Siglecs are a family of proteins widely expressed on inn

146 Siglecs are Ig-superfamily lectins on mammalian leukocyt

147 The majority of Siglecs are inhibitory receptors expressed in immune cel

148 their ligands, we speculated that the B cell siglecs are key players in tolerance induced by DST.

149 e that also expresses Siglec ligands, B cell Siglecs are recruited to the immunological synapse, resu

150 Siglecs are sialic acid-binding Ig-like lectins that rec

151 ic-acid-binding immunoglobulin-like-lectins (siglecs) are expressed in human pancreatic islets in a c

152 d on recent findings showing that the B cell siglecs, CD22 and Siglec-G, can promote tolerance to Ags

153 CD33-related Siglecs (CD33rSiglecs) on innate immune cells recognize

154 ic acid-binding immunoglobulin-like lectins (Siglecs) consists of immunomodulatory molecules that hav

155 ligands that bind to inhibitory CD33-related Siglecs could provide novel targets for cancer immunomod

156 neutrophil activation in a sialic acid- and Siglec-dependent manner.

157 ented TLR4 ligand-induced disruption of TLR4:Siglec E/F interactions.

158 In vivo imaging showed that siglec-E also promoted ROS in acutely inflamed lungs fol

159 In contrast, the mouse homolog Siglec-E binds to murine LGALS3BP with lower affinity.

160 Removal of Siglec-E causes the development of exaggerated signs of

161 -1 recruitment between dimeric and monomeric Siglec-E expressed on HEK293A cells.

162 ken together, these results demonstrate that siglec-E functions as an inhibitory receptor of neutroph

163 Thus, we further investigated the impact of Siglec-E homodimerization.

164 ranslocation to cell surface to disrupt TLR4:Siglec-E interaction.

165 Siglec-E is a sialic acid-binding Ig-like lectin express

166 We show that Siglec-E is required for Escherichia coli-induced endocy

167 Although all antibodies detected Siglec-E on transfected human HEK-293T cells, only two r

168 ition to form a disulfide bridge between two Siglec-E polypeptides.

169 Here, we demonstrate that siglec-E promoted neutrophil production of reactive oxyg

170 Siglec-E promotion of ROS was likely mediated via Akt ac

171 by replacing the inhibitory domain of mouse Siglec-E with the activating module of Siglec-16.

172 s, and only two antibodies recognized native Siglec-E within spleen lysates.

173 cation has complex effects on recognition by Siglec-E, in relationship to the underlying structures.

174 the functionally equivalent human paralog of Siglec-E, occurs as a monomer.

175 keeping with this, we show that mice lacking Siglec-E, the main member of the CD33rSiglec family, exh

176 ta relating to the structure and function of Siglec-E, the major CD33-related Siglec expressed on mou

177 lomonocytic Siglecs in vivo we studied mouse Siglec-E, the murine functional equivalent of Siglec-9.

178 rat monoclonal antibodies specific to mouse Siglec-E, with no cross-reactivity to Siglec-F.

179 Siglec-E-deficient dendritic cells infected with E. coli

180 result of the inability to internalize TLR4, Siglec-E-deficient dendritic cells were also defective f

181 In keeping with this, Siglec-E-deficient macrophages showed a propensity towar

182 Siglec-E-deficient mice also showed enhanced immunosurve

183 Siglec-E-deficient mice showed increased in vivo killing

184 itic cells from wild-type mice, but not from Siglec-E-deficient mice, after E. coli infection.

185 tumors were established, they grew faster in Siglec-E-deficient mice.

186 likely mediated via Akt activation, because siglec-E-deficient neutrophils plated on fibrinogen exhi

187 Moreover, whereas all antibodies recognized Siglec-E-Fc on immunoblots, binding was dependent on int

188 features that Sia-antigen imposed on DCs are Siglec-E-mediated and maintained under inflammatory cond

189 PH oxidase inhibitor, apocynin, reversed the siglec-E-mediated suppression of neutrophil recruitment

190 Importantly, siglec-E-promoted ROS were required for its inhibitory f

191 Siglec-E16 enhanced proinflammatory cytokine expression

192 Notably, Siglec-engaging antigenic liposomes formulated with an h

193 function of Siglec-E, the major CD33-related Siglec expressed on mouse neutrophils, monocytes, macrop

194 ormal mice induced the recruitment of CD11b+ Siglec F+ Ly-6G(lo) Ly-6C(neg) CCR3+ eosinophils to the

195 ic acid-binding, immunoglobulin-like lectin (Siglec) F is a glycan-binding protein selectively expres

196 lic acid-binding immunoglobulin-like lectin (Siglec)-F is a proapoptotic receptor on mouse eosinophil

197 Proteomic analysis of Siglec-F binding material identified Muc5b and Muc4.

198 Siglec-F human IgG1 fusion protein (Siglec-F-Fc) was use

199 that attenuation of ST3Gal-III will decrease Siglec-F ligand levels and enhance allergic eosinophilic

200 ilic airway inflammation and less sialylated Siglec-F ligands in their airways.

201 Expression of sialoadhesin and Siglec-F ligands increased, and that of CD22 ligands dec

202 500-kDa and approximately 200-kDa candidate Siglec-F ligands that were less abundant in St3gal3(+/-)

203 After OVA sensitization and challenge, Siglec-F ligands were increased in wild-type mouse lungs

204 d in vitro and in vivo for the expression of Siglec-F ligands.

205 ion protein (Siglec-F-Fc) was used to detect Siglec-F ligands.

206 se (ST3Gal-III) is required for constitutive Siglec-F lung ligand synthesis.

207 that levels of sialylated airway ligands for Siglec-F might be diminished in mice with attenuated lev

208 Siglec-F recognizes sialylated sulfated glycans in glyca

209 ransition from a Siglec-F(med) CD11c(-) to a Siglec-F(high) CD11c(low) phenotype in lung tissue was a

210 Gradual transition from a Siglec-F(med) CD11c(-) to a Siglec-F(high) CD11c(low) ph

211 1b(+) DC lineage, including CD101, TREM1 and Siglec-F, and shows that the absence of CD103(+)CD11b(+)

212 Western blotting and cytochemistry used Siglec-F-Fc as a probe for directed purification, follow

213 Western blotting with Siglec-F-Fc detected approximately 500-kDa and approxima

214 Siglec-F human IgG1 fusion protein (Siglec-F-Fc) was used to detect Siglec-F ligands.

215 trol lung eosinophilia through engagement of Siglec-F.

216 tity of Muc5b as one glycoprotein ligand for Siglec-F.

217 mouse Siglec-E, with no cross-reactivity to Siglec-F.

218 ected mouse lung glycoproteins that bound to Siglec-F; binding was sialic acid dependent.

219 sive and direct interactions between TLR and Siglec families of pattern recognition receptors.

220 n example of a paired receptor system in the Siglec family has multiple implications for regulation o

221 ctates tight specificity distinct from other Siglec family members and any other endogenous glycan re

222 Ig-like lectin (Siglec)-G are members of the Siglec family of inhibitory coreceptors expressed on B c

223 r of the sialic acid-binding Ig-like lectin (Siglec) family expressed on all B cells.

224 CD22, a sialic acid-binding Ig-type lectin (Siglec) family member, is an inhibitory coreceptor of th

225 r of the sialic acid-binding Ig-like lectin (Siglec) family, is expressed on B cell and dendritic cel

226 were defined as IL-5-dependent peribronchial Siglec-FhiCD62L-CD101hi cells with a segmented nucleus.

227 monary rEos are IL-5-independent parenchymal Siglec-FintCD62L+CD101lo cells with a ring-shaped nucleu

228 ses predicted that only some human and mouse Siglecs form disulfide-linked dimers.

229 Modulators of Siglec function are likely to be developed and investiga

230 Many Siglecs function as inhibitory receptors on innate and a

231 Most CD33-related Siglecs function as inhibitory receptors, but the abilit

232 we addressed the question of whether loss of Siglec G on its own affects disease severity in animal m

233 -surface proteins, including BTLA, IRF4, and Siglec G.

234 CD22 and sialic acid-binding Ig-like lectin (Siglec)-G are members of the Siglec family of inhibitory

235 Mechanistic studies with various relevant Siglec-G and CD24 knockout mice and chimeric animals, al

236 eous autoimmunity, mice double-deficient for Siglec-G and the related Siglec protein CD22 did show au

237 he inhibitory functions of CD22/Siglec-2 and Siglec-G and their contributions to tolerance and autoim

238 CD22 and Siglec-G are recruited to the immunological synapse by s

239 mpartment, demonstrating the crucial role of Siglec-G as an inhibitory receptor on this cellular subs

240 Mouse Siglec-G did not show appreciable binding to any TLRs te

241 to be associated with autoimmunity, loss of Siglec-G does not result in autoimmune disease in BALB/c

242 We report that Siglec-G expression on host APCs, specifically on hemato

243 all cells display sialic acids, and CD22 and Siglec-G have distinct, yet overlapping, specificities f

244 In this study, we analyzed the role of Siglec-G in induction and maintenance of B cell toleranc

245 Siglec-G is a member of the sialic acid-binding Ig-like

246 These results indicate that Siglec-G is important to maintain tolerance in B cells a

247 an autoimmune-prone MRL/lpr background that Siglec-G is important to maintain tolerance in B cells.

248 Thus, the loss of the inhibitory receptor Siglec-G led to a moderate exacerbation of disease sever

249 ouse RBCs are essentially devoid of CD22 and Siglec-G ligands.

250 trate that enhancing the interaction between Siglec-G on host APCs with CD24 on donor T cells attenua

251 However, there is evidence from Siglec-G x CD22 double-deficient mice and Siglec-G(-/-)

252 We find that aging Siglec-G-deficient and Siglec-G x FcgammaRIIb double-deficient mice develop an

253 ss of the inhibitory receptor FcgammaRIIb in Siglec-G(-/-) mice does not result in exacerbation of di

254 om Siglec-G x CD22 double-deficient mice and Siglec-G(-/-) mice on an autoimmune-prone MRL/lpr backgr

255 c-acid-binding immunoglobulin-like lectin-G (Siglec-G) by noninfectious damage-associated molecular p

256 Siglec-G, a member of the sialic acid-binding Ig-like le

257 gs showing that the B cell siglecs, CD22 and Siglec-G, can promote tolerance to Ags presented on the

258 e 1 (SHP1) or membrane receptors CD22 and/or Siglec-G, result in enhanced BCR signaling and decreased

259 Taken together, our data demonstrate that Siglec-G-CD24 axis, controls the severity of GVHD and su

260 Although both Siglec-G-deficient and control MRL/lpr mice developed a

261 We find that aging Siglec-G-deficient and Siglec-G x FcgammaRIIb double-def

262 Moreover, Siglec-G-deficient female mice showed a significantly re

263 Although Siglec-G-deficient mice did not develop spontaneous auto

264 Aging Siglec-G-deficient mice have elevated numbers of plasma

265 Siglec-G-deficient mice show a large expansion of the B1

266 cell activation, especially on B1 cells, as Siglec-G-deficient mice show mainly a B1 cell-restricted

267 Siglec-G-deficient mice showed moderately increased clin

268 The Siglec-G-deficient mouse was also backcrossed to the aut

269 MRL/lpr mice developed a lupus-like disease, Siglec-G-deficient MRL/lpr mice showed an earlier occurr

270 c STAT1(-/-) BM demonstrated increased CD9(-)Siglec H(hi) plasmacytoid dendritic cells (pDCs), and de

271 the type I IFN, IFN-alpha, in vitro and that Siglec-H knockout (KO) mice produce more IFN-alpha after

272 In contrast, uninfected aging Siglec-H KO mice developed a mild form of systemic autoi

273 several weeks after a single mCMV infection, Siglec-H KO mice developed a severe form of systemic lup

274 autoimmune disease after virus infection in Siglec-H KO mice was accompanied by a type I IFN signatu

275 These results show that Siglec-H normally serves as a modulator of type I IFN re

276 retion of type I IFN of pDCs is modulated by Siglec-H, a DAP12-associated receptor on pDCs.

277 In this study, we show that Siglec-H-deficient pDCs produce more of the type I IFN,

278 Immunomodulation by Siglecs has been extensively studied, but relationships

279 Siglecs have been best studied in the tumor context in a

280 entified impact of inhibitory myelomonocytic Siglecs in cancer biology, with distinct roles that refl

281 indicating a secondary role of CD33-related Siglecs in limiting cancer-promoting inflammation and tu

282 te the function of inhibitory myelomonocytic Siglecs in vivo we studied mouse Siglec-E, the murine fu

283 Because up-regulation of Siglec ligands in cancer tissue has been observed, the c

284 These results demonstrate that the lack of Siglec ligands on the surface of murine RBCs permits B c

285 ate Ag on a cell surface that also expresses Siglec ligands, B cell Siglecs are recruited to the immu

286 lic acid-binding immunoglobulin-like lectin (siglec) ligands.

287 genetic approaches, we show that the B cell siglecs mediate tolerance to cell surface Ags by initiat

288 l responses to erythrocyte Ags and show that Siglec-mediated B cell tolerance is restricted to cell t

289 ouble-deficient for Siglec-G and the related Siglec protein CD22 did show autoimmunity at an older ag

290 immunoglobulin superfamily lectin receptors (Siglecs) provide negative regulation.

291 ic acid-binding Ig-like lectin (Siglec)-7, a siglec receptor expressed on DCs that mediates rapid end

292 aising the possibility that these are paired Siglec receptors that balance immune responses to pathog

293 human microglia, including TLR, Fcgamma and SIGLEC receptors, as well as TAL1 and IFI16, regulators

294 Since mice do not have paired Siglec receptors, we generated a model by replacing the

295 hibitory sialic acid-binding Ig-like lectin (Siglec) receptors, and enhanced binding to the NK-activa

296 uman Siglec-9 and for other immunomodulatory Siglecs, such as Siglec-5 and Siglec-10.

297 CD169 is a Siglec that may function as an adhesion molecule and a f

298 K cells are prominent examples of inhibitory Siglecs that can potentially dampen anti-tumor immunity.

299 lic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell l

300 Of note, CD33 is the only Siglec with a peroxisome-targeting sequence, and this mo