ライフサイエンスコーパス: IL-15R

1 ion of the high-affinity receptor for IL-15, IL-15R alpha, on T cells is dispensable for the generati

2 of the homeostatic pathway defined by IL-15/IL-15R (IL-15 receptor) interaction and the inflammasome

3 provide novel insights into the use of IL-15/IL-15R alpha complexes to relieve tumor-resident T cells

4 re, we report that in vivo delivery of IL-15/IL-15R alpha complexes triggers rapid and significant re

5 ipheral blood following treatment with IL-15/IL-15R alpha complexes, the destruction of solid tumors

6 sue expression of IL-2/IL-2R alpha and IL-15/IL-15R alpha differ.

7 tence of two autocrine loops involving IL-15/IL-15R and IL-2/IL-2R, both contributing to the spontane

8 that the total number and duration of IL-15/IL-15R complexes on the cell surface crosses a quantitat

9 omputational results demonstrated that IL-15/IL-15R complexes on the cell surface were a key determin

10 trol the formation and localization of IL-15/IL-15R complexes.

11 from costimulation blockade might be a IL-15/IL-15R dependent process.

12 cells in vivo seem to utilize only the IL-15/IL-15R homeostatic pathway, although the proliferative r

13 In the absence of IL-7R signaling, IL-15/IL-15R interaction is dispensable for the production of

14 ing small-molecule inhibitors impeding IL-15/IL-15R interaction.

15 e have demonstrated that targeting the IL-15/IL-15R pathway represents a new and potent strategy to p

16 Targeting the IL-15/IL-15R pathway represents a potent strategy to prevent r

17 blockade might represent a CD8(+) and IL-15/IL-15R(+)-dependent process.

18 These findings suggest that 1) IL-15/IL-15R+ cells are crucial to these T cell-dependent immu

19 diseases associated with expression of IL-15/IL-15R.

20 a and IL-2R gamma c in the presence of IL-2, IL-15R alpha did not co-precipitate with the IL-2R beta/

21 Despite a marked expansion of IL-2/IL-15R beta(+) cells in lymphoid organs and peripheral b

22 ly diminished expression of CD122, the IL-2R/IL-15R beta-chain, and impaired expression of the T-box

23 ll expansion and acquisition of CD45RO+IL-7R+IL-15R+ phenotype.

24 t inhibit IL-15 binding to its high affinity IL-15R.

25 ty to present IL-15 in trans to low-affinity IL-15R beta gamma(c) receptors on memory CD8(+) T cells.

26 Interleukin-15 receptor alpha (IL-15R alpha) is a pleiotropically expressed molecule th

27 common gamma (C gamma ) chain, IL-7R alpha , IL-15R alpha; and proliferative responses of T cells in

28 tion and maturation, expression of IL-15 and IL-15R alpha by both parenchymal and hematopoietic cells

29 We analyzed the requirements for IL-15 and IL-15R alpha expression by bone marrow-derived or parenc

30 Studies conducted in IL-15- and IL-15R knockout mice identified IL-15 as an important cy

31 genes encoding interferon- alpha , IL-2, and IL-15R alpha (P < .05, for each).

32 nt cross-linking to affinity label IL-2R and IL-15R on YT cells and OKT3 blasts.

33 ry CD8 T cells also down-regulated IL-7R and IL-15R expression and failed to undergo homeostatic prol

34 in lymphoid organs, the levels of IL-7R and IL-15R expression likely set a threshold for the homeost

35 rways gradually lost expression of IL-7R and IL-15R, did not respond to IL-7 and/or IL-15, and exhibi

36 hain, which is shared with IL-7R, IL-9R, and IL-15R.

37 ctional similarities between IL-2R alpha and IL-15R alpha chains, the activation-triggered mechanisms

38 eraction between maIL-15 expressed by DC and IL-15R on CD4(+) T cells results in one pathway and the

39 egated according to the expression of CD122 (IL-15R) in that only the central memory CD8(+) T cells w

40 kin (IL)-15, and IL-15 receptor alpha chain (IL-15R alpha ) were associated with the magnitude of the

41 By contrast, IL-15R alpha expression on cells other than T cells is a

42 report, we show that the recently described IL-15R(alpha) subunit cooperates with IL-2Rbeta gamma(c)

43 After memory CD8(+) T cell differentiation, IL-15R alpha expression on DCs selectively supports cent

44 ha and show that NK cells rely upon distinct IL-15R alpha dependent IL-15 signals than memory CD8(+)

45 NK cells, and CD4+ and CD8+ T cells express IL-15R alpha chains.

46 onstrate that resting human NK cells express IL-15R(alpha) mRNA and further, that picomolar amounts o

47 induces proliferation of cells co-expressing IL-15R alpha, IL-2R beta, and IL-2R gamma chains.

48 We found IL-15R alpha mRNA expression in IL-15-stimulated and Ag-

49 unexpected results provide insights into how IL-15R alpha supports memory CD8(+) T cells.

50 The results suggest the existence of a human IL-15R alpha subunit, although physical evidence of this

51 To study the expression of human IL-15R alpha chains, we have utilized tagged human IL-15

52 15Ralpha on NK cells substantially increased IL-15R complex formation and accelerated the expansion o

53 sporine or rapamycin, blocks mitogen-induced IL-15R alpha expression.

54 Despite secretion of IL-15, LCs lack IL-15R-alpha for surface presentation of IL-15.

55 we have generated four lines of mice lacking IL-15R alpha in various cell types.

56 By contrast, mice lacking IL-15R alpha on macrophages, DCs, or both, exhibit equiv

57 nding and receptor internalization modulated IL-15R occupancy.

58 expression of IL-15R alpha and IL-15 but not IL-15R beta.

59 LCs synthesize the highest amounts of IL-15R-alpha mRNA and protein, which binds IL-15 for pre

60 in vivo and the potential for destruction of IL-15R+ leukocytes, we examined the immunosuppressive ac

61 ffinity receptors, supports the existence of IL-15R alpha on these cells.

62 completely on parenchymal cell expression of IL-15R alpha and IL-15 but not IL-15R beta.

63 ne unique roles for macrophage expression of IL-15R alpha and show that NK cells rely upon distinct I

64 ed cell proliferation following knockdown of IL-15R alpha expression.

65 sufficient for IL-15 binding, regulation of IL-15R alpha expression may represent a new target for T

66 sive function help to understand the role of IL-15R expression on endothelium, and further support a

67 udy suggests that the effective targeting of IL-15R-triggered events with CRB-15 can be of therapeuti

68 s in addition to its private binding protein IL-15R(alpha) in T-cells.

69 'downstream' of the interleukin 15 receptor (IL-15R) and through the transcription factor Id2.

70 IL-15 function and to target IL-15 receptor (IL-15R) bearing cells, we have generated a unique lytic

71 d by IL-15, the influence of IL-15 receptor (IL-15R)-mediated signaling at the cellular level has not

72 IL-15 and the IL-15 receptor (IL-15R)alpha chain are essential for normal development

73 ribed unique features of the IL-15 receptor (IL-15R)alpha.

74 ion most likely involved the alpha receptor (IL-15R alpha) because this high affinity receptor would

75 exing this cytokine to its soluble receptor, IL-15R alpha.

76 hereas memory-phenotype CD8 T cells required IL-15R alpha expression only by hematopoietic cells.

77 Naive CD8 T cell development required IL-15R alpha expression by both bone marrow-derived and

78 Since IL-15R alpha chain is necessary and sufficient for IL-15

79 L-2, and an IL-15-specific receptor subunit, IL-15R alpha.

80 e of the IL-15 proliferative signal and that IL-15R occupancy functioned as an effective surrogate me

81 We find that IL-15R alpha expression on macrophages but not dendritic

82 , express high levels of CD44, B220, and the IL-15R/IL-2R, and undergo fas-dependent apoptosis.

83 s a result of the very low expression of the IL-15R in this population of cells in the absence of the

84 Additional characterization of the IL-15R utilized covalent cross-linking to affinity label

85 e also evaluated the effect of PGE(2) on the IL-15R complex that consists of IL-2Rbeta, common gamma-

86 We therefore studied the IL-15R alpha chain expression in human gamma delta T cel

87 udy we examined the effects of targeting the IL-15R on the prevention and treatment of collagen-induc

88 a2a fusion protein (CRB-15) that targets the IL-15R.

89 tant IL-15 proteins specifically bind to the IL-15R, competitively inhibit IL-15-triggered cell proli

90 These findings may be related to IL-15R alpha's ability to present IL-15 in trans to low-

91 ates in this context through the traditional IL-15R.

92 s of the IL-2R in combination with an unique IL-15R alpha chain.

93 n of CD122 and CD127, molecules that make up IL-15R and IL-7R, respectively, than other memory T cell

94 ports central memory CD8(+) T cells, whereas IL-15R alpha expression on macrophages supports both cen

95 However, whether IL-15R alpha expression by these subsets is necessary fo

96 To investigate whether IL-15R alpha presented by different cells perform distin

97 impeding the association of IL-2R beta with IL-15R.

98 vity increased over time in correlation with IL-15R alpha gene expression.

99 n of antigenic peptides, which together with IL-15R-alpha/IL-15, break tolerance against WT1 by stimu