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 16a and a membrane-bound interleukin (IL)-15/IL-15R fusion protein.

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

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

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

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

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

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

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

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

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

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

13 dition, we introduced a membrane-bound IL-15/IL-15R fusion protein to promote in vivo persistence.

14 emCD8TCs) is thought to be mediated by IL-15/IL-15R heterodimer (15HD)-expressing myeloid cells.

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

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

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

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

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

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

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

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

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

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

25 e for MAIT17 differentiation, while the IL-2/IL-15R-mTORC1-T-bet axis ensures MAIT1 differentiation.

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

27 onstrate unique long-lived CD44(hi) IL-7R(+) IL-15R(+) CD4(+) memory T cells in both retina and secon

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

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

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

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

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

33 etinol acyltransferase gene and bred onto an IL-15R-KO (15R-KO) genetic background (L15R) that expres

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

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

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

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

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

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

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

41 This was evidenced by reduced IL-7R and IL-15R levels but increased CD5 and Nur77 expression.

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

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

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

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

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

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

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

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

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

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

52 C maintenance is mediated by 15HD, not empty IL-15R, 15HD content in L15R mice was determined and fou

53 ccur independently, and although AP enhances IL-15R assembly, it has no significant effect on IL-15 s

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

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

56 KO) genetic background (L15R) that expressed IL-15R in HSCs at normal levels, but not in other liver

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

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

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

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

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

62 15Ralpha on NK cells substantially increased IL-15R complex formation and accelerated the expansion o

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

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

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

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

67 The low IL-15R expression in the bone marrow (BM) of L15R mice w

68 Outside of the liver of L15R mice, IL-15R expression was found in a number of organs, but n

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

94 on of the transcription factor Eomes and the IL-15R subunit CD122, known positive regulators of T(VM)

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

96 and humans, expressing the beta-chain of the IL-15R complex (CD122) and responding to IL-15.

97 idence for the intercellular assembly of the IL-15R heterotrimer exists.

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

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

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

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

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

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

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

105 ILC3s coexpressing all three IL-15R subunits (IL15Ra/B/y) increased following bacteri

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

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

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

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

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

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

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

113 ered a genetically engineered mouse in which IL-15R complementary DNA (cDNA) had been inserted in-fra

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

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

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