ライフサイエンスコーパス: IL-17R

1 IL-17R deficiency conferred a reduction in neutrophil nu

2 IL-17R knockout (KO) mice displayed a significant delay

3 IL-17R signaling is critical for pulmonary neutrophil re

4 IL-17R(-/-) mice demonstrated systemic antimicroflora Ab

5 IL-17R(-/-) mice developed a normal adaptive immunity ag

6 IL-17R-deficient mice were exquisitely sensitive to intr

7 IL-17R:Fc (50-200 microg/ml) markedly inhibited T cell p

8 IL-17R:Fc for 6 days decreased MNC infiltration in the i

9 IL-17R:Fc or control human immunoglobulin G was administ

10 IL-17R:Fc or control IgG was added at the start of mouse

11 Accordingly, the IL-17-IL-17R axis may provide an attractive target for the man

12 Elevated levels of IL-17A, IL-17R, IFN-gamma, IL-12Rbeta1, IL-2, IL-13, IL-6, IL-1b

13 els of intestinal pIgR and IgA in B6.IL-17R (IL-17R(-/-)) mice were lower than wild type mice.

14 leukin 23 (IL-23), IL-1 receptor I (IL-1RI), IL-17R, tissue inhibitors of metalloproteinase 1 and 2 (

15 ngly dependent on the interleukin-23 (IL-23)/IL-17R axis, as mice and humans with defects in IL-17R s

16 r signaling domain was identified within all IL-17Rs, termed similar expression to fibroblast growth

17 SEFIR, this extension is not conserved among IL-17R family members.

18 reveal distinct signaling differences among IL-17R family members.

19 This suggests an IL-17R-mediated signaling pathway rather than an IL-17-i

20 These results support an IL-17R-mediated signaling pathway involving JAK and NF-k

21 e to call these molecules IL-17, vIL-17, and IL-17R, respectively.

22 Th17-deficient (IL-23p19(-/-)) and IL-17R-deficient (IL-17RA(-/-)) mice experienced severe

23 r expression to fibroblast growth factor and IL-17R; Toll-IL-1R)-related signaling molecules, such as

24 ession to fibroblast growth factor genes and IL-17R (SEFIR).

25 Moreover, when TRAF6 and IL-17R were coexpressed in 293 cells, TRAF6 coimmunoprec

26 ession to fibroblast growth factor genes and IL-17Rs (SEFIR) domain of IL-17RC, but the SEFIR is esse

27 urthermore, treatment with neutralizing anti-IL-17R antibody ablated the enhanced survival observed i

28 A and IL-17F were blocked by a specific anti-IL-17R Ab, but only IL-17A was blocked with a soluble IL

29 rom chronic destructive arthritis similar as IL-17R-/- -->IL-17R-/- chimeras.

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

31 nhibited in mice that were deficient in both IL-17R and IFN-gammaR compared with wild-type animals.

32 nd Il17ra(-/-)Itgb2(-/-) mice that lack both IL-17R and all four beta(2) integrins.

33 ted that hBD-2 stimulation was attenuated by IL-17R-specific Ab, but not by IL-1R antagonist or the n

34 tended significantly from 10.5 to 19 days by IL-17R:Fc (500 microg/day; days 0-6).

35 Thus, OECs dominantly control IL-17R-dependent responses to OPC through regulation of

36 to the knee joint of naive IL-17R-deficient (IL-17R-/-) mice had no effect on the acute phase of arth

37 Chimeric mice of host wt and donor IL-17R-/- BM cells developed destructive synovitis in th

38 12a(+/-) mice was due to enhanced downstream IL-17R signaling.

39 o experimental autoimmune encephalomyelitis, IL-17R-signaling-deficient mice demonstrated earlier dis

40 nship between the gut microbiota and enteric IL-17R signaling that controlled dysbiosis, constrained

41 row (BM) chimeric mice revealed the need for IL-17R expression on radiation-resistant joint cells for

42 y cells in human lung tissue, and functional IL-17R signaling occurs on the basolateral surface of hu

43 estructive arthritis similar as IL-17R-/- -->IL-17R-/- chimeras.

44 In contrast, chimeric mice of host IL-17R-/- and donor wt BM cells were protected from chro

45 These data support impaired IL-17R signaling as a potential mechanism by which defic

46 However, neutralization of IL-10 activity in IL-17R(-/-) mice failed to provide protection.

47 d in IFN-gammaR(-/-) but is less affected in IL-17R(-/-) recipients.

48 n response to the K. pneumoniae challenge in IL-17R KO mice.

49 17R axis, as mice and humans with defects in IL-17R signaling (IL17F, ACT1, IL-17RA) or in genes that

50 g infection in mice genetically deficient in IL-17R or in mice overexpressing a soluble IL-17R.

51 of IL-17 in IFN-gammaR(-/-) or IFN-gamma in IL-17R(-/-) mice further suppresses the adoptive transfe

52 t the development of tumors was inhibited in IL-17R-deficient mice.

53 Indeed, IL-17R(-/-) and IL-22(-/-) mice displayed impaired bacte

54 Infected IL-17R-deficient corneas had low intercellular adhesion

55 Rasgrp1-deficient mice lacking IL-17R had fewer germinal centers, and germinal centers

56 Mechanistically, IL-17R interacts with NOTCH1 via the extracellular domai

57 oluble IL-17R, suggesting that cell membrane IL-17R is required for signaling by both IL-17A and IL-1

58 Using Il-17ra(-/-) mice, IL-17R signaling in cells other than LSK(-) cells was fo

59 wall) directly into the knee joint of naive IL-17R-deficient (IL-17R-/-) mice had no effect on the a

60 Namely, IL-17Rs contain a conserved SEF/IL-17R (SEFIR) subdomain

61 or C (IL-17RC), and adaptor protein Act1 (of IL-17R) all had reduced demyelination accompanied by les

62 Functional studies with mice deficient of IL-17R, IL-17A, and IL-17F further revealed that IL-17 s

63 Conditional deletion of IL-17R in the enteric epithelium demonstrated that there

64 Disruption of IL-17R signaling in the enteric epithelium resulted in S

65 Finally, HSV infection of IL-17R knockout mice as well as IL-17 neutralization in

66 CH1 activation results in the interaction of IL-17R adaptor Act1 with NICD1, followed by the transloc

67 Irrespective of IL-17R:Fc treatment for either 6 days or continuously, a

68 receptor complexes consisting of members of IL-17R family.

69 macrophages in the hapten challenged skin of IL-17R(-/-) recipients is significantly reduced whereas

70 okines, and collagenase-3 in the synovium of IL-17R-/- mice.

71 At baseline, the hemopoietic system of IL-17R knockout mice (IL-17Ra(-/-)) is, with the excepti

72 and susceptibility is strongly dependent on IL-17R signaling.

73 (+) T cells is reduced in IFN-gammaR(-/-) or IL-17R(-/-) mice compared with WT controls.

74 hapten-challenged skin of IFN-gammaR(-/-) or IL-17R(-/-) recipients compared with WT controls.

75 properties that are nonredundant with other IL-17R family members.

76 neumoniae inoculation and that IL-23 p19-/-, IL-17R-/-, and IL-12 p35-/- mice also show increased sus

77 of MCPIP1 on IL-6, IkappaBzeta, and possibly IL-17R subunits results in a biologically relevant inhib

78 iciency in IL-23, IL-17A, or IL-17 receptor (IL-17R) and mAb neutralization of CXCR2, the p19 subunit

79 Signaling through the IL-17 receptor (IL-17R) is required to prevent oropharyngeal candidiasis

80 Furthermore, the levels of IL-17 receptor (IL-17R) on the TRAF6-deficient EFs were comparable to th

81 the adaptor protein Act1 in IL-17 receptor (IL-17R) signaling and IL-17-dependent immune responses.

82 Interleukin-17 (IL-17) and IL-17 receptor (IL-17R) signaling are essential for regulating mucosal h

83 We hypothesized that IL-17 receptor (IL-17R) signaling is critical for G-CSF and CXC chemokin

84 srupting IL-17 production or IL-17 receptor (IL-17R) signaling.

85 itin ligase, is recruited to IL-17 receptor (IL-17R) upon IL-17 stimulation and is required for IL-17

86 m wild-type mice, those from IL-17 receptor (IL-17R)-deficient mice had significantly lower corneal p

87 F were rendered sensitive in IL-17 receptor (IL-17R)-knockout hosts deficient in T(H)17 effector func

88 le of interleukin-17 (IL-17)/IL-17 receptor (IL-17R)-mediated signaling in the protective immunity ag

89 (CXCR2) nor interleukin-17 (IL-17) receptor (IL-17R) deficiency changed the severity of disease follo

90 17 mediates inflammation through a receptor (IL-17R) composed of two subunits, IL-17RA and IL-17RC.

91 SEF/IL-17R/CIKS/ACT1 homology (SEFIR) domain containing prot

92 Namely, IL-17Rs contain a conserved SEF/IL-17R (SEFIR) subdomain that engages Act1, leading to a

93 We demonstrate that the intracellular Sef/IL-17R (SEFIR) domain of IL-17RD targets TIR adaptor pro

94 in IL-17RC(-/-) fibroblasts required the SEF/IL-17R signaling domain (SEFIR), a conserved motif commo

95 -23 and was critical for host defense, since IL-17R-deficient mice had a phenotype similar to that of

96 L-17D.2, IL-17E, IL-17B, and IL-17C) and six IL-17R genes (IL-17RA.1, IL-17RA.2, IL-17RA.3, IL-17RF,

97 , but only IL-17A was blocked with a soluble IL-17R, suggesting that cell membrane IL-17R is required

98 n IL-17R or in mice overexpressing a soluble IL-17R.

99 These data strongly indicate that IL-17R signaling in radiation-resistant cells in the joi

100 In the present study, we report that IL-17R signaling is required in radiation-resistant cell

101 Bone marrow transplantation revealed that IL-17R expression on nonhemopoietic cells had the greate

102 In this study, we show that IL-17R is localized to basal airway cells in human lung

103 Our data show that IL-17R signaling in the lung epithelium plays a critical

104 The IL-17R deficiency increased CD8 T cell infiltration, whe

105 ignal transduction pathways activated by the IL-17R have not been characterized.

106 38 MAPK-independent pathway that couples the IL-17R with enhanced mRNA stability.

107 The signature cytokine, IL-17, engages the IL-17R and recruits the E3-ligase NF-kappaB activator 1

108 minor proportion of CD11c+ DC expressed the IL-17R.

109 involving cross-regulation of members of the IL-17R and TLR families.

110 , the configuration and stoichiometry of the IL-17R complex remain unknown.

111 mponent is IL-17RC, a distinct member of the IL-17R family.

112 To interrogate the role of the IL-17R in OECs, we generated mice with conditional delet

113 dy provides the first structural view of the IL-17R intracellular signaling, unraveling the mechanism

114 , and demonstrates the essential role of the IL-17R on keratinocytes in driving disease pathogenesis.

115 lammation through the distinct impact of the IL-17R-Act1 and IL-25R-Act1 axes.

116 , recruitment of Act1 to IL-17R required the IL-17R conserved cytoplasmic 'SEFIR' domain, followed by

117 In this study, we show that the IL-17R adaptor protein Act1/CIKS is involved in this pro

118 IL-17Rh1, a protein distantly related to the IL-17R, suggesting that IL-17E probably possesses unique

119 restricted to activated T cells, whereas the IL-17R is expressed in a variety of cell types including

120 suggesting that IL-17RA subunits within the IL-17R complex undergo a conformational change upon liga

121 uggesting a negative feedback effect through IL-17R.

122 IL-17A-producing Tn cell populations through IL-17R.

123 Thus, IL-17R signaling is critical for optimal production of G

124 imulation with IL-17, recruitment of Act1 to IL-17R required the IL-17R conserved cytoplasmic 'SEFIR'

125 domain (SEFIR), a conserved motif common to IL-17R family members.

126 Administering DSS to IL-17R(-/-) mice resulted in increased weight loss and m

127 dentified in an EST data base by homology to IL-17R, was found to bind specifically IL-17B, as determ

128 itin ligase, and mediates its recruitment to IL-17Rs.

129 L-17A on circulating neutrophil levels using IL-17R-deficient (Il17ra(-/-)) mice and Il17ra(-/-)Itgb2

130 gh the interactions of IL-17A or IL-17F with IL-17R was confirmed in splenocyte cultures in vitro.

131 n 293 cells, TRAF6 coimmunoprecipitated with IL-17R.