ライフサイエンスコーパス: IL-10R

1 IL-10R blockade maintained IL-12 protein 40, markedly in

2 IL-10R blockage abolished PPAR-gamma-mediated inhibition

3 IL-10R deficiency was confirmed by functional assays on

4 c domain of the receptor for interleukin 10 (IL-10R) contains two box 3 sequence motifs that have bee

5 cently identified the interleukin-10 (IL-10)/IL-10R pathway as a key regulator of acute versus chroni

6 ction, as neutralizing antibodies for IL-10, IL-10R, and TGF-beta were unable to revert suppression,

7 ectional IL-10-dependent loop, then an IL-10-IL-10R pathway defect could abrogate the anti-inflammato

8 In this way, a genetic IL-10-IL-10R pathway defect could interact with an environment

9 Thus, a functional IL-10-IL-10R pathway was essential for 1,25-(OH)(2)D(3) to inh

10 ce from lethal intestinal damage in an IL-10-IL-10R-dependent manner.

11 ing in inhibition of the interleukin (IL)-10/IL-10R autocrine/paracrine cytokine autoregulatory loop

12 Because the defect in patients with IL-10/IL-10R deficiency resides in hematopoietic lineage cells

13 We sought to gather clinical data of IL-10/IL-10R-deficient patients and devise guidelines for diag

14 IL-10/IL-10R-deficient patients had intractable enterocolitis,

15 Medical records of IL-10/IL-10R-deficient patients were reviewed and compiled.

16 s directly recruited to the ligand-activated IL-10R by binding to specific phosphotyrosine groups whi

17 est the existence of at least one additional IL-10R subunit.

18 nits: IFN-alpha R beta L, IFN-gamma R alpha, IL-10R alpha, IL-2R beta, and IL-4R alpha.

19 Therapeutic administration of an IL-10R blocking Ab enhanced control of the recrudescent

20 nal disease should be screened for IL-10 and IL-10R deficiency and that allogeneic HSCT can induce re

21 fied loss of function mutations in IL-10 and IL-10R in patients with very early onset IBD.

22 the lungs, whereas IFN-gamma, TNF-alpha, and IL-10R remain unchanged from wild type.

23 in experimental visceral leishmaniasis, and IL-10R blockade represents a potential immuno- and/or im

24 d in normal alveolar epithelium of mice, and IL-10R were constitutively expressed on normal murine AM

25 Anti-IL-10R blocks RMTC-mediated modulation of EAE and suppre

26 Anti-IL-10R mAb treatment further suppressed parasite growth

27 Anti-IL-10R therapy reversed the tolerogenic effects of the d

28 ocytes treated in vitro with anti-IL-10/anti-IL-10R were unable to protect recipient mice from develo

29 Furthermore, administration of an anti-IL-10R mAb to unmanipulated adult mice was sufficient to

30 evels of IL-10 were neutralized with an anti-IL-10R mAb.

31 Neutralizing anti-IL-10 and anti-IL-10R, but not anti-TGF-beta, anti-IL-4, or anti-CTLA-4

32 However, because anti-IL-10R also released IFN-gamma-independent effects, IL-1

33 urther and dramatically reduced in both anti-IL-10R-treated IL-4R alpha(-/-) mice and IL-4R alpha x I

34 T cells, and regulation was reversed by anti-IL-10R antibody.

35 IL-10 signaling was blocked (either by anti-IL-10R mAb treatment or by using IL-10-deficient mice).

36 , inflammation in H. hepaticus-infected anti-IL-10R-treated mice, demonstrating a pathogenic role for

37 normal mice with established infection, anti-IL-10R treatment was remarkably active, inducing near-cu

38 T cell-dependent colitis, one involving anti-IL-10R monoclonal antibody treatment of infected T cell-

39 However, in IFN-gamma knockout mice, anti-IL-10R also induced both granuloma formation and leishma

40 nist 1-methyltryptophan or neutralizing anti-IL-10R from days 12 to 21 after DC10 therapy partially r

41 -10(+/+) mice treated with neutralizing anti-IL-10R monoclonal antibody were able to survive lethal c

42 Administration of anti-IL-10R Ab into GM-CSF-treated mice abrogated GM-CSF-indu

43 In contrast, coadministration of anti-IL-10R and TGF-beta mAbs had little effect upon parasite

44 Th1 recall responses in the presence of anti-IL-10R mAb, as removal of LPS abrogated this effect.

45 sive transfer with either anti-IL-10 or anti-IL-10R mAb.

46 In fact, systemic anti-IL-10R Ab treatment prevented viral reactivation in up t

47 Upon systemic anti-IL-10R Ab treatment, we observed a significant expansion

48 blockade studies in mice revealed that anti-IL-10R mAb treatment during acute infection modestly inc

49 monstrate in this study using transient anti-IL-10R treatment that it is the presence of IL-10 in viv

50 tide antigen administered together with anti-IL-10R and LPS.

51 findings were made in mice treated with anti-IL-10R antibody and infected with RSV.

52 th factor (TGF)-beta, as treatment with anti-IL-10R but not anti-TGF-beta monoclonal antibody abrogat

53 rmal mice treated prophylactically with anti-IL-10R demonstrated accelerated granuloma assembly and r

54 llowing BCG vaccination concurrent with anti-IL-10R mAb treatment was sustained through chronic M. tu

55 in IL-4Ralpha(-/-) mice, treatment with anti-IL-10R mAb virtually eliminated L. major parasites in bo

56 IL-4R alpha(-/-) mice were treated with anti-IL-10R mAb, and in a genetic approach, the IL-4R alpha(-

57 letion or treatment of BALB/c mice with anti-IL-10R mAb.

58 e protein antigen was administered with anti-IL-10R mAb; however, this was not the case with peptide

59 r, Pi3k-gamma(-/-) mice pretreated with anti-IL-10R were resistant to C. jejuni-induced intestinal in

60 ing were performed on mice treated with anti-IL-10R-blocking Ab at 3, 6, and 9 d postinfection (dpi)

61 he defined IL-10R, which we now designate as IL-10R alpha.

62 iologic responses only to hIL-10 by both BaF-IL-10R transfectants and normal human peripheral blood c

63 reversed by adding neutralizing Abs to both IL-10R and TGF-beta2.

64 The mucosa-specific protection afforded by IL-10R blockade was associated with an increased accumul

65 As judged by IL-10R blockade, endogenous IL-10 primarily regulates ki

66 ent immune regulation, partially mediated by IL-10R-signaling, prevented enhanced disease.

67 T-cell reactivation and not sensitization by IL-10R(-/-) DCs leads to enhanced CHS.

68 cmvIL-10 were investigated, and the classic IL-10R/JAK1/Stat3 pathway was found to be activated in m

69 In contrast, IL-10R(-/-) DCs produced increased levels of proinflamma

70 impaired in its ability to bind the defined IL-10R, which we now designate as IL-10R alpha.

71 ninflammatory hemopoietic cells also express IL-10Rs.

72 CD138(+) MPhi expressed IL-10R, CD206, and CCR2 but little TNF-alpha or CX3CR1.

73 everity in the absence of IL-10 or following IL-10R blockade.

74 s well as native retina expressed functional IL-10R as determined by immunoblot analysis and by the a

75 enitor promyeloid cells expressed functional IL-10Rs, as assessed by precipitation of a 110-kDa prote

76 Hence, IL-10R deficiency is associated with a high risk of deve

77 COS-1 cells, co-expressing the human IL-10R and individual STAT proteins, confirmed a prefere

78 llectively, our studies define innate immune IL-10R signaling as a key factor regulating mucosal immu

79 tion and IL-1beta secretion was abrogated in IL-10R-deficient macrophages.

80 y TLRs was not associated with a decrease in IL-10R expression, but did require expression of the mye

81 ti-inflammatory macrophages were observed in IL-10R-deficient patients with very early onset inflamma

82 LR2, TLR4, or TLR9 was sufficient to inhibit IL-10R signal transduction, including phosphorylation an

83 Instead, IL-10R blockade increased intratumoral dendritic cell ex

84 Interestingly, IL-10R blockade during acute RSV infection altered CD4(+

85 to both hIL-10 and vIL-10 require the known IL-10R, and suggest the existence of at least one additi

86 Expression of the regulatory molecules IL-10R, SIRP-alpha/beta, CD47, CD200R, and CD200L was me

87 otifs, as shown by the analysis of the mouse IL-10R constructs containing progressively truncated cyt

88 the rat retinal sections to identify native IL-10R.

89 ress CD4(+) T cells with a dominant-negative IL-10R.

90 significantly inhibited with a neutralizing IL-10R Ab.

91 The similar actions of IL-10R and IL-6R on the induction of endogenous IL-6-res

92 se observations establish that activation of IL-10R promotes survival of RGCs and this survival-promo

93 Blockade of IL-10R by Ab or genetic deficiency of IL-10 resulted in

94 Blockade of IL-10R converted a chronic LCMV infection into a rapidly

95 Interestingly, in vivo blockade of IL-10R did not affect GM-CSF-induced expansion of CD4(+)

96 ls within the liver, and in vivo blockade of IL-10R resulted in a decreased percentage of intrahepati

97 losis-susceptible CBA/J mice, Ab blockade of IL-10R specifically during BCG vaccination resulted in a

98 tudy, we have determined the contribution of IL-10R signaling to the regulation of immune responses d

99 Importantly, the pathogenic effects of IL-10R blockade during P. berghei ANKA infection were re

100 Our findings underscore the importance of IL-10R signaling in preventing T-cell- and cytokine-medi

101 While infusion of IL-10R blocking antibody, initiated at day 60, caused a

102 Inhibition of IL-10R function by TLRs was not associated with a decrea

103 findings demonstrate that internalization of IL-10R with the resultant impact on IL-10 signaling and

104 findings demonstrate that internalization of IL-10R with the resultant impact on IL-10 signaling and

105 protein kinase Cbeta and internalization of IL-10R, and was independent of TLR2 and phagocytosis.

106 Moreover, loss of IL-10R signaling impaired the generation and function of

107 itro experiments confirmed reconstitution of IL-10R-mediated signaling in all patients who received t

108 require the two membrane-distal tyrosines of IL-10R, but Stat3 appears to function only in the anti-p

109 This process is dependent on IL-10R-mediated STAT3 signaling, as supported by the lac

110 ach, we identified 16 patients with IL-10 or IL-10R deficiency: 3 patients had mutations in IL-10, 5

111 nhibit EAE in mice with a disrupted IL-10 or IL-10R gene.

112 pendent and was abrogated by Abs to IL-10 or IL-10R.

113 the binding of Jak1 to IFN-alpha R beta L or IL-10R alpha.

114 crease in survival in IL-10 knockout mice or IL-10R-blocked B6 mice after IL-12 plus IL-18 treatment.

115 as preformed to identify the IL-10 receptor (IL-10R) and phosphorylated or nonphosphorylated Akt and

116 c interleukin-10 (IL-10) and IL-10 receptor (IL-10R) deficiencies cause very early onset severe infla

117 erved internalization of the IL-10 receptor (IL-10R) in mucosal lymphocytes, which could limit cellul

118 ted deficiencies of IL-10 or IL-10 receptor (IL-10R) lead to immune dysregulation with life-threateni

119 mal mice, anti-interleukin (IL)-10 receptor (IL-10R) monoclonal antibody (MAb) treatment induced intr

120 blockade in vitro with anti-IL-10 receptor (IL-10R) monoclonal antibody restored LPMC IFN-gamma and

121 cobacter hepaticus plus anti-IL-10 receptor (IL-10R) monoclonal antibody was exacerbated by co-admini

122 Interleukin-10 receptor (IL-10R) signaling is considered to be a vital component

123 Intact interleukin-10 receptor (IL-10R) signaling on effector and T regulatory (Treg) ce

124 and therapeutic blockade of IL-10 receptor (IL-10R) was equivalent to CSF-1 neutralization in enhanc

125 In vivo blockade of the IL-10 receptor (IL-10R) with a neutralizing antibody resulted in rapid r

126 Blockade of IL-10 receptor (IL-10R) with an antagonist antibody dramatically reduced

127 ed IL-10R1, a subunit of the IL-10 receptor (IL-10R), and also SOCS3, a negative regulator of proinfl

128 back mechanism involving the IL-10 receptor (IL-10R).

129 DC-specific deletion of the IL-10 receptor (IL-10R).

130 was absent or overexpressed or its receptor (IL-10R) was blockaded.

131 ely 1000-fold lower affinity for recombinant IL-10R than does hIL-10, yet stimulates proliferation of

132 soluble TNFR:Fc fusion protein, and soluble IL-10R were used.

133 al TG-resident CD8(+) T cells, but also that IL-10R blockade might have therapeutic potential to redu

134 ansduction through the IL-10R on AM and that IL-10R function can be inhibited by stimulation of Toll-

135 expressing interferon gamma, suggesting that IL-10R signaling limits effector T cell differentiation.

136 The IL-10R, together with reporter gene constructs containin

137 ion of the inhibitory cytokine IL-10 and the IL-10R are sustained after induction of LPS tolerance.

138 IL-22 does not bind the IL-10R.

139 ide insight into cytokine recognition by the IL-10R family and highlight the plasticity of type III i

140 ated in hepatoma cells stably expressing the IL-10R.

141 sion of CXCL9 and -16 failed to occur if the IL-10R was blocked in vivo, an intervention associated w

142 6)) located in the cytoplasmic domain of the IL-10R alpha chain were required for receptor function,

143 show that antibody-mediated blockade of the IL-10R during P. berghei ANKA infection in ECM-resistant

144 The signaling capabilities of the IL-10R for activating specific STAT proteins and inducin

145 STAT proteins, confirmed a preference of the IL-10R for STAT3 and STAT1.

146 Surface expression of the IL-10R is transiently up-regulated on CD8 T cells follow

147 ing involves tyrosine phosphorylation of the IL-10R JAK1 (Janus kinase) and TYK2 (tyrosine kinase) re

148 r results revealed an unexpected role of the IL-10R pathway in lymphomagenesis.

149 These data establish that activation of the IL-10R promotes survival of progenitor myeloid cells.

150 environment, we found that expression of the IL-10R was required only on CD8(+) T cells to facilitate

151 nfection of IL-10(-/-) mice, blockade of the IL-10R, or depletion of CD25(+) cells during the chronic

152 pendent of C-terminal serine residues of the IL-10R, previously shown to be required for other anti-i

153 ate their signals via the STAT3 pathway, the IL-10R appears unique in promoting a potent anti-inflamm

154 Unlike many hematopoietin receptors, the IL-10R did not detectably activate STAT5.

155 The data demonstrate that the IL-10R, unlike other members of the interferon receptor

156 ulatory T cells and on signaling through the IL-10R and correlated with global downregulation of DC i

157 , stimulates signal transduction through the IL-10R on AM and that IL-10R function can be inhibited b

158 ation of a 110-kDa protein with an Ab to the IL-10R and by the ability of IL-10 to activate Jak1 and

159 ect was inhibited by neutralizing Abs to the IL-10R.

160 way dependent on STAT3 but not unique to the IL-10R.

161 To determine whether the IL-10R has signaling functions similar to IL-6R in cells

162 Coinjection of nt-nls-MmGFP with the IL-10R Tyr(446) and Tyr(496) amino-acid residues complet

163 Therapeutic IL-10R blockade broke the cycle of IL-10-mediated immune

164 When mAb to TGFbeta1 or to IL-10R was administered at the time of challenge, the re

165 nts with IL-10 deficiency and 1 patient with IL-10R alpha chain deficiency and proved to be an effect

166 induce sustained remission in 1 patient with IL-10R deficiency.

167 the lack of an IL-10 effect in patients with IL-10R deficiency and dominant-negative STAT3 mutation.

168 neic HSCT can induce remission in those with IL-10R deficiency.