ライフサイエンスコーパス: IL-12R

1 IL-12R beta 2 is not expressed by naive resting CD4+ T c

2 IL-12R beta 2 mRNA levels from LPS-challenged IRF-2(-/-)

3 IL-12R beta 2(-/-) splenocytes were deficient in IFN-gam

4 nit primarily responsible for binding IL-12, IL-12R beta 2 plays an essential role in mediating the b

5 ex vivo to increase CD25 levels, and IL-12, IL-12R, and STAT4, but not the NK activating receptor Ly

6 for ILC2 plasticity was mapped to the IL-12-IL-12R signaling pathway and was confirmed through analy

7 ve immune maturation by modulating the IL-12/IL-12R pathway and the novelty of the OT-II.Ncf1(m1J) mo

8 IL-12/IL-12R/STAT4 signaling promotes the development of EAM.

9 Two subunits of the IL-12 receptor (IL-12R), IL-12R beta 1 and IL-12R beta 2, have been identified an

10 pically expressed the IL-12 receptor-beta 2 (IL-12R beta 2) bicistronically with enhanced green fluor

11 The IL-12 receptor-beta 2 (IL-12R beta 2) chain is expressed on Th1 cells and lost

12 heterodimer for binding to the high affinity IL-12R and inhibits IL-12 bioactivity in vitro.

13 e mediated through a specific, high affinity IL-12R composed of an IL-12Rbeta1/IL-12Rbeta2 heterodime

14 fore, IL-12, in binding to the high affinity IL-12R, interacts with IL-12Rbeta1 primarily via regions

15 emonstrate that the functional high-affinity IL-12R is composed of at least two beta-type cytokine re

16 n the regulation of not only IL-12, but also IL-12R.

17 sting that both diminished IL-12 and altered IL-12R expression contribute to the paucity of IFN-gamma

18 g abnormality that reduces IL-12R beta 1 and IL-12R beta 2 expression in tuberculosis.

19 and anti-TGF-beta enhanced IL-12R beta 1 and IL-12R beta 2 expression, and IFN-gamma production.

20 IL-10 and TGF-beta reduced IL-12R beta 1 and IL-12R beta 2 expression, as well as IFN-gamma productio

21 is, and that expression of IL-12R beta 1 and IL-12R beta 2 may play a central role in mediating a pro

22 measured expression of the IL-12R beta 1 and IL-12R beta 2 subunits, as well as IL-12R beta 2 mRNA ex

23 ages of T cells expressing IL-12R beta 1 and IL-12R beta 2 were significantly decreased, and IL-12R b

24 e IL-12 receptor (IL-12R), IL-12R beta 1 and IL-12R beta 2, have been identified and cloned.

25 responses, whereas SNPs within the IL-10 and IL-12R genes were associated with low antibody and lymph

26 ed in Th1 development (IFN-gamma, T-bet, and IL-12R).

27 12R beta 2 were significantly decreased, and IL-12R beta 2 mRNA expression was also markedly reduced.

28 significantly reduced in IFN-gamma(-/-) and IL-12R beta 2(-/-) recipient mice suggesting that the ro

29 ted the expression of CD28, CD40 ligand, and IL-12R by Ag-activated primary T cells from DO11.10 (OVA

30 e approximately 100-bp IFN-gamma TCR-RE, and IL-12R signaling also stimulates TCR-induced activity of

31 Conversely, IFN-gamma synthesis and IL-12R synthesis were rescued by the addition of exogeno

32 eta 1 and IL-12R beta 2 subunits, as well as IL-12R beta 2 mRNA expression in tuberculosis patients a

33 B6.TNFR2-/- and B6.IL-12R-/- mice treated with costimulation blockade plus

34 ction in supernatants of MLC using either B6.IL-12R(-/-) or control B6 responder cells.

35 induced wasting disease in recipients of B6.IL-12R(-/-) CD4(+) spleen cells that received a TNF inhi

36 ve responses of B6.129S1-IL-12rb2(tm1Jm) (B6.IL-12R(-/-)) responder spleen cells were found to be com

37 Th1 T cell responses, in addition to blunted IL-12R expression and severely attenuated proinflammator

38 (CD4+)CD28- IL-12R+ cells responded to IL-12 stimulation with the up

39 -12 to convert Th2 cells bearing a competent IL-12R to the Th1 cells, we showed that: (a) T cells bea

40 In contrast, IL-12R beta 1 deficiency did not significantly alter the

41 Rapamycin did not affect DC IL-12R expression, but markedly suppressed IL-18Ralpha a

42 gamma production was not caused by decreased IL-12R expression because the STAT4 S721 mutant also fai

43 , we have generated IL-12R beta 2-deficient (IL-12R beta 2(-/-)) mice by targeted mutation in embryon

44 important regulators of Th1 differentiation, IL-12R and T-bet, also are not required for acquisition

45 ulation of Th2 cells expressing this ectopic IL-12R beta 2 in the presence of IL-12 led to levels of

46 3 binds to IL-12R beta 1 but fails to engage IL-12R beta 2; nonetheless, IL-23 activates Stat4 in PHA

47 ients, anti-IL-10 and anti-TGF-beta enhanced IL-12R beta 1 and IL-12R beta 2 expression, and IFN-gamm

48 , in which IFN-gamma production is enhanced, IL-12R beta 2 mRNA expression was also increased.

49 e basis for this selective loss, we examined IL-12R beta 2 subunit expression during Th cell developm

50 cally maintain IL-12 responsiveness, express IL-12R beta 2 mRNA, and can stimulate nitric oxide produ

51 duced, the percentages of T cells expressing IL-12R beta 1 and IL-12R beta 2 were significantly decre

52 For IL-12R studies, reverse transcription-PCR and 125I-IL-12

53 Although Con A-activated splenocytes from IL-12R beta 2(-/-) mice still bind IL-12 with both high

54 Furthermore, IL-12R beta 2(-/-) mice were deficient in vivo in their

55 beta 2 in IL-12 signaling, we have generated IL-12R beta 2-deficient (IL-12R beta 2(-/-)) mice by tar

56 Regulation of the factors governing IL-12R expression and IL-12 responsiveness has been show

57 s of hulL-12 with these two identified human IL-12R protein subunits are examined.

58 have reclassified the previously identified IL-12R beta subunit as huIL-12R beta 1 and designated th

59 Coexpression of the two identified IL-12R subunits in Ba/F3 cells conferred IL-12 responsiv

60 Changes in IL-12R mRNA were associated with increased IFN-gamma sec

61 such synthesis is associated with increased IL-12R beta2-chain expression as well as STAT4 intracell

62 IL-4 inhibited IL-12R beta 2 expression leading to the loss of IL-12 si

63 We investigated IL-12R expression and function in human infectious disea

64 tral conditions, BALB/c T cells rapidly lose IL-12R beta2 expression, STAT4 phosphorylation, and func

65 LB/c x B10.D2) DO11.10 CD4+ T cells maintain IL-12R beta 2 expression when stimulated similarly.

66 ent of early developing Th2 cells maintained IL-12R beta 2 expression and restored the ability of the

67 ription by at least two separate mechanisms; IL-12R signaling without TCR signaling targets promoter

68 hese results demonstrate that although mouse IL-12R beta 1 is the subunit primarily responsible for b

69 Human and mouse IL-12R beta 2 proteins show a 68% amino acid sequence id

70 50 pM, although a role for endogenous mouse IL-12R beta 1 in IL-12 signal transduction in these tran

71 ough different mechanisms, neither IL-4R nor IL-12R has any clear advantage in polarizing cells; rath

72 chain transgene (and thus capable of normal IL-12R expression and signaling) to undergo Th1 differen

73 Although IL-4 receptors (IL-4Rs) but not IL-12Rs are expressed on naive CD4(+) T cells, IL-4 has

74 a R alpha and beta-chains, in the absence of IL-12R components.

75 NK lytic activity of IL-12R beta 2(-/-) splenocytes was not induced when incu

76 h1/Th2 development may be the attenuation of IL-12R beta 2 expression.

77 response to IL-12 through downregulation of IL-12R expression and in part through inhibition of APC

78 In this study, we examined the effect of IL-12R beta 1 and IFN-gamma deficiency on the developmen

79 n human tuberculosis, and that expression of IL-12R beta 1 and IL-12R beta 2 may play a central role

80 me lineage attributes, such as expression of IL-12R beta 2 (interleukin 12 receptor beta 2), required

81 The expression of IL-12R beta 2 in Th2 cells did not lead to significant l

82 Expression of IL-12R mRNA was not restricted to lymph node T cells, an

83 This paper reports the expression of IL-12R on a human gamma delta T cell line that responds

84 feration, IFN-gamma production, induction of IL-12R expression, triggering of pathogenicity, and expr

85 ly, the PGE2- and DXM-mediated inhibition of IL-12R expression was not affected significantly by addi

86 Finally, levels of IL-12R beta 2 subunit mRNA and the percent composition o

87 y IFN-gamma mRNA, demonstrating that loss of IL-12R results in diminished IL-12 responsiveness.

88 More efficient maintenance of IL-12R beta2 expression by B10.D2 T cells activated unde

89 -12/STAT4 responses through up-regulation of IL-12R expression and synergized with IL-12 in driving T

90 To investigate the role of IL-12R beta 2 in IL-12 signaling, we have generated IL-1

91 Con A-activated splenocytes of IL-12R beta 2(-/-) mice failed to produce IFN-gamma or p

92 ied EAE in mice deficient in this subunit of IL-12R.

93 Expression of IL-12Rs is one important checkpoint for Th1 development.

94 hrough a mechanism not dependent on TNFR2 or IL-12R signaling.

95 TCR plus IL-12R stimulation of effector Th cells resulted in: 1)

96 e exhibit reduced IL-12R expression and poor IL-12R signaling function.

97 a 1 and beta 2 chains of the IL-12 receptor (IL-12R) and tyrosine phosphorylate STAT4 in response to

98 lts from a selective loss of IL-12 receptor (IL-12R) beta 2 subunit expression.

99 imulated via the FcR and the IL-12 receptor (IL-12R) exhibited enhanced levels of activated STAT4 and

100 as involved in the arrest of IL-12 receptor (IL-12R) IL-12Rbeta1, but not IL-12Rbeta2, in the membran

101 lts- We examined the role of IL-12 receptor (IL-12R) signaling in the development of murine experimen

102 f IgG (FcgammaRIIIa) and the IL-12 receptor (IL-12R), both constitutively expressed on NK cells.

103 Two subunits of the IL-12 receptor (IL-12R), IL-12R beta 1 and IL-12R beta 2, have been iden

104 e previously identified IL-12 beta receptor (IL-12R beta) protein, two classes of 125I-huIL-12 bindin

105 plasmic regions of interleukin-12 receptors (IL-12R) beta1 and beta2 in stimulating proliferation was

106 tors, recombinant IL-10 and TGF-beta reduced IL-12R beta 1 and IL-12R beta 2 expression, as well as I

107 T cells from STAT4(-/-) mice exhibit reduced IL-12R expression and poor IL-12R signaling function.

108 AMP), or cholera toxin substantially reduced IL-12R expression, suggesting that PGE2 may be mediating

109 n is the underlying abnormality that reduces IL-12R beta 1 and IL-12R beta 2 expression in tuberculos

110 B subunits of enterotoxin adjuvants regulate IL-12R expression and subsequent Th cell subset response

111 2 and dexamethasone (DXM) have in regulating IL-12R expression was evaluated.

112 shown to have a prominent role in regulating IL-12R expression.

113 expression of the IL-12R signaling subunit, IL-12R beta2, and with IL-12-induced STAT4 phosphorylati

114 not the CT-A/LT-B chimera or nLT, suppressed IL-12R expression and IFN-gamma production by activated

115 ption factor T-bet and its downstream target IL-12R beta2, independently of IFN gamma.

116 Our findings provide evidence that IL-12R expression correlates well with IFN-gamma product

117 These results suggest that IL-12R signaling affects IFN-gamma gene transcription by

118 Thus, although the IL-12R beta 2 and IL-12-dependent STAT4 activation are r

119 periments revealed that FcgammaRIIIa and the IL-12R colocalized to areas of lipid raft microdomains i

120 hat dual recruitment of FcgammaRIIIa and the IL-12R to lipid raft microdomains allows for enhanced ac

121 to increase expression of both CD25 and the IL-12R, thus providing positive cross-regulation of rece

122 ostimulation of NK cells via the FcR and the IL-12R.

123 IL-12 signaling can be localized between the IL-12R complex and Stat4.

124 e and to PHA-activated PBMC that express the IL-12R, thus demonstrating cytokine receptor specificity

125 patients for the presence of message for the IL-12R beta 1 and beta 2 genes using RNase protection as

126 re uncharacterized intracellular form of the IL-12R (termed "isoform 2") that presumably has limited

127 2R expression, we measured expression of the IL-12R beta 1 and IL-12R beta 2 subunits, as well as IL-

128 in neutral conditions lose expression of the IL-12R beta 2 subunit and become unresponsive to IL-12.

129 Th2 cells, they expressed low levels of the IL-12R beta 2 subunit and retained the ability to differ

130 Controlling the expression of the IL-12R beta 2 subunit could be an important therapeutic

131 The expression of the IL-12R beta1- and beta2-chains on T cells and NK cells f

132 To gain further knowledge of the IL-12R complex and the IL-12 signal transduction pathway

133 sted showed mRNA accumulation for one of the IL-12R components, IL-12 binding sites were detected in

134 onsiveness correlated with expression of the IL-12R signaling subunit, IL-12R beta2, and with IL-12-i

135 Two chains of the IL-12R, IL-12Rbeta1 and IL-12Rbeta2, have recently been

136 or IL-12 through increased expression of the IL-12R-signaling subunit (IL-12Rbeta2) on T cells activa

137 Th2 T cells express only the IL-12R beta 1 and thus do not tyrosine phosphorylate STA

138 Previous studies demonstrated that the IL-12R beta 1 subunit was required for mouse T and NK ce

139 Q/J mice did not signal normally through the IL-12R and manifested a defect in their capacity to phos

140 a and was dependent on signaling through the IL-12R expressed on CD25(-) responder cells, but not on

141 ade was independent of signaling through the IL-12R, but it was reduced further by coblockade of CD70

142 Like IL-12, IL-23 binds to the IL-12R subunit IL-12Rbeta1.

143 These IL-12R individually bind huIL-12 with low affinity and i

144 40)2 does not block high affinity binding to IL-12R on PHA-activated human lymphoblasts.

145 IL-23 binds to IL-12R beta 1 but fails to engage IL-12R beta 2; nonethe

146 Two IL-12R proteins, designated human IL-12 (huIL-12) recept

147 e between the cytoplasmic regions of the two IL-12R subunits and JAK2/Tyk2 and that the cytoplasmic r

148 administration of exogenous IL-12 upregulate IL-12R expression in BALB/c mice, while the neutralizati

149 Th1 response in tuberculosis correlated with IL-12R expression, we measured expression of the IL-12R

150 Interestingly, Ba/F3 cells transfected with IL-12R beta 2 alone proliferated in response to huIL-12