ライフサイエンスコーパス: GILT

1 GILT activates LLO within the phagosome by the thiol red

2 GILT expression levels progressively increase in T cells

3 GILT facilitated the processing and presentation to anti

4 GILT facilitates unfolding of endocytosed antigens in MH

5 GILT is a soluble thiol reductase expressed constitutive

6 GILT is essential for cross-presentation of a CD8+ T cel

7 GILT is synthesized as a 35-kDa precursor, and following

8 GILT may be important in disulfide bond reduction of pro

9 GILT plays a crucial role in unfolding the antigenic pro

10 GILT(-/-) mice are phenotypically normal, but their T ce

11 GILT(-/-) mice were relatively resistant to MOG(35-55)-i

12 GILT-/- peripheral T cells express reduced levels of mit

13 GILT-tagged GAA was significantly more effective than rh

14 GILT-tagged GAA was taken up by L6 myoblasts about 25-fo

15 ed the mouse homolog of GILT and generated a GILT knockout mouse.

16 T reconstituted MHC class II processing of a GILT-dependent HEL epitope.

17 s(49) abrogated MHC class II processing of a GILT-dependent HEL epitope.

18 ts for GILT in MHC class II Ag processing, a GILT-deficient murine B cell lymphoma line was generated

19 ly outside the cell, as enzymatically active GILT is secreted by activated macrophages.

20 included large numbers of plasma cells; and GILT(-/-) T cells proliferated to peptides other than MO

21 Surprisingly, comparison of wild-type and GILT-deficient T cell activation in vitro revealed stron

22 as one of the key intermediaries affected by GILT expression in fibroblasts.

23 Tumor cell GILT expression was partially restored with IFN-gamma tr

24 MHC class II genes and the processing enzyme GILT in human melanomas.

25 They further imply mechanisms for GILT-independent reduction in the late endosome, with GI

26 To define the functional requirements for GILT in MHC class II Ag processing, a GILT-deficient mur

27 g in, lysosomes, suggesting a novel role for GILT in cells of the macrophage lineage.

28 In summary, our results suggest a role for GILT in maintaining cysteine cathepsin proteolytic effic

29 imental particles confirmed a major role for GILT in phagosomal disulfide reduction in both resting a

30 Furthermore, a few unexpected roles for GILT have been uncovered: as a host factor for Listeria

31 show that both cytokines are sufficient for GILT induction in the absence of a microbial stimulus.

32 to our knowledge, previously unreported, for GILT in the maintenance of tolerance to TRP1.

33 Furthermore, GILT-deficient mice have a 4-fold increase in the percen

34 HSV-1 infection, or cross-priming, is highly GILT-dependent, as is initiation of the response to the

35 However, GILT is necessary for presentation of either epitope whe

36 ndertook the present studies to determine if GILT(-/-) mice would process exogenously administered my

37 ide bonds and are presented on MHC class II, GILT is likely to be important in the pathogenesis of ot

38 WT rat MOG-immunized mice, rat MOG-immunized GILT(-/-) mice generated Abs that transferred EAE to MOG

39 n early phagosomal proteolytic efficiency in GILT-deficient macrophages, specifically in the absence

40 Even though MOG(35-55) was immunogenic in GILT(-/-) mice, GILT APCs could not generate MOG(35-55)

41 Replication of the organism in GILT-negative macrophages, or macrophages expressing an

42 ophages expressing an enzymatically inactive GILT mutant, is impaired because of delayed escape from

43 ssing and presentation components, including GILT.

44 1 plays a direct role in IFN-gamma-inducible GILT expression.

45 ntigens requires a complex pathway involving GILT-mediated reduction, unfolding, and partial proteoly

46 Mice lacking GILT are deficient in generating major histocompatibilit

47 Both precursor and mature GILT reduce disulfide bonds with an acidic pH optimum.

48 le for cathepsin S in the turnover of mature GILT and in regulating levels of mature cathepsin L prot

49 OG(35-55) was immunogenic in GILT(-/-) mice, GILT APCs could not generate MOG(35-55) from MOG protein

50 lyses demonstrated that wild-type and mutant GILT were expressed and maintained lysosomal localizatio

51 melanomas expressed relatively little to no GILT protein or mRNA.

52 Treg cells partially restores the ability of GILT-deficient TRP1-specific CD4(+) T cells to induce vi

53 ctivity of SOD2 is reduced in the absence of GILT because of reduced SOD2 protein stability.

54 cific T cells that develop in the absence of GILT have diminished IL-2 and IFN-gamma production.

55 The absence of GILT in melanomas altered antigen processing and the hie

56 peripheral T cells develop in the absence of GILT or TRP1, demonstrating that GILT is required for ne

57 ncrease in SOD2 expression in the absence of GILT restores fibroblast proliferation to wild-type leve

58 In the absence of GILT, CD4-positive T cell responses to Der p 1 are signi

59 lls escape thymic deletion in the absence of GILT, they are tolerant to TRP1 and do not induce viliti

60 ed stronger responsiveness in the absence of GILT.

61 ide evidence that the mechanism of action of GILT resembles that of other thiol oxidoreductases.

62 nstrate that the thiol reductase activity of GILT is its essential function in MHC class II-restricte

63 The effect of GILT in reducing the proliferative and cytotoxic respons

64 he current study was to assess the effect of GILT on major phagosomal functions with an emphasis on p

65 ecursor GILT and decreases the efficiency of GILT maturation.

66 elivered to the lysosome, the mature form of GILT-tagged GAA was indistinguishable from rhGAA and per

67 Precursor forms of GILT-bearing mutations in Cys(200) or Cys(211), previous

68 Here, we identified the mouse homolog of GILT and generated a GILT knockout mouse.

69 Immunization of GILT(-/-) mice with rat MOG protein resulted in a switch

70 erentiation, to investigate the induction of GILT upon exposure to bacteria.

71 processing have shown that the influence of GILT on the peptide repertoire can alter the character o

72 hages, constitutively express high levels of GILT, although the pathways regulating its expression in

73 The majority of GILT synthesized by differentiated THP-1 cells is secret

74 duced with wild-type and cysteine mutants of GILT.

75 tes are centrally deleted in the presence of GILT and TRP1.

76 The presence of GILT confers a small increase in the percentage of autor

77 These data suggest that regulation of GILT expression may be a mechanism of T cell differentia

78 The increased sensitivity of GILT-deficient T cells results in a more severe hypergly

79 The active site of GILT contains two cysteine residues in a CXXC motif that

80 o analysis has shown that the active site of GILT involves Cys(46) and Cys(49), present in a CXXC mot

81 Several studies of GILT and antigen processing have shown that the influenc

82 s have greatly expanded our understanding of GILT's function.

83 eron-induced lysosomal transferase-positive (GILT+) CD1a-/CD123- dendritic cells.

84 e show that, like its mature form, precursor GILT reduces disulfide bonds with an acidic pH optimum,

85 s disulfide-linked dimerization of precursor GILT and decreases the efficiency of GILT maturation.

86 We also show that processing of precursor GILT can be mediated by multiple lysosomal proteases and

87 ive site facilitates processing of precursor GILT to the mature form.

88 genes required for class II Ag presentation, GILT was not regulated by CIITA.

89 bs that transferred EAE to MOG(35-55)-primed GILT(-/-) mice, and these Abs bound to oligodendrocytes.

90 In addition, purified GILT activates recombinant LLO, facilitating membrane pe

91 II editor HLA-DM, lysosomal thiol-reductase GILT, and a 47-kDa enolase-like protein.

92 N-gamma-inducible lysosomal thiol reductase (GILT) display increased sensitivity to TCR ligation.

93 mma-IFN-inducible lysosomal thiol reductase (GILT) facilitates major histocompatibility complex class

94 mma-IFN-inducible lysosomal thiol reductase (GILT) facilitates the generation of class II-binding pep

95 N-gamma-inducible lysosomal thiol reductase (GILT) functions to catalyze thiol bond reduction, thus u

96 erferon-inducible lysosomal thiol reductase (GILT) has been the only enzyme described in the endosome

97 N-gamma-inducible lysosomal thiol reductase (GILT) is a unique thiol reductase with optimal enzymatic

98 Gamma interferon-inducible thiol reductase (GILT) is an enzyme involved in the initial steps of anti

99 N-gamma-inducible lysosomal thiol reductase (GILT) is an enzyme located in the Lamp-2-positive compar

100 erferon-inducible lysosomal thiol reductase (GILT) is constitutively expressed in antigen-presenting

101 erferon-inducible lysosomal thiol reductase (GILT) is constitutively present in late endocytic compar

102 erferon-inducible lysosomal thiol reductase (GILT) is known to reduce disulfide bonds present in prot

103 mma-IFN-inducible lysosomal thiol reductase (GILT) is present in the MHC class II loading compartment

104 erferon-inducible lysosomal thiol reductase (GILT) to a mature thiol reductase, but suggest a role fo

105 erferon-inducible lysosomal thiol reductase (GILT), a thioredoxin-related oxidoreductase, functions i

106 erferon-inducible lysosomal thiol reductase (GILT), constitutively expressed in antigen-presenting ce

107 N-gamma-inducible lysosomal thiol reductase (GILT), the only reductase thus far known to be involved

108 N-gamma-inducible lysosomal thiol reductase (GILT), which plays a role in MHC class II-restricted pro

109 erferon-inducible lysosomal thiol reductase (GILT).

110 erferon-inducible lysosomal thiol reductase (GILT, also called Ifi30) is responsible for the activati

111 Mass spectral analysis also revealed GILT's ability to reduce cysteinylated epitopes.

112 ycosylation-independent lysosomal targeting (GILT) tag, which contains a portion of insulin-like grow

113 In this study, we demonstrate that GILT is expressed in T lymphocytes and that it has an AP

114 absence of GILT or TRP1, demonstrating that GILT is required for negative selection of TRP1-specific

115 Finally, we provide evidence that GILT is required for optimal activity of the lysosomal c

116 Here, we show that GILT also facilitates MHC class I-restricted recognition

117 The data show that GILT is a critical host factor that facilitates L. monoc

118 Here, we show that GILT is required for class II-restricted processing and

119 Recently we have shown that GILT is also expressed in mouse T cells, where it exerts

120 We show in this study that GILT is required for efficient MHC class II-restricted p

121 The GILT-tagged GAA enzyme may provide an improved enzyme re

122 terferon-inducible lysosomal thiolreductase (GILT) promotes major histocompatibility complex (MHC) cl

123 Thus, GILT appears to have a fundamental role in cellular prol

124 Thus, GILT has a critical role in regulating CD4(+) T-cell tol

125 Transduction with wild-type GILT reconstituted MHC class II processing of a GILT-dep

126 Unlike GILT induction in response to IFN-gamma treatment, induc

127 pendent reduction in the late endosome, with GILT perhaps being reserved for more intractable Ags.