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 expression was enriched in thymic APCs capable of m

4 GILT facilitated MHC class II-restricted presentation of

5 GILT facilitated the processing and presentation to anti

6 GILT facilitates unfolding of endocytosed antigens in MH

7 GILT is a soluble thiol reductase expressed constitutive

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

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

10 GILT may be important in disulfide bond reduction of pro

11 GILT plays a crucial role in unfolding the antigenic pro

12 GILT protein expression in melanocytes was induced in ha

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

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

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

16 GILT-tagged GAA was significantly more effective than rh

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

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

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

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

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

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

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

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

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

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

27 Using bone marrow chimeras, GILT expression in thymic epithelial cells (TECs), but n

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

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

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

31 These studies support a role for GILT and the MHC class II Ag presentation pathway in mel

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

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

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

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

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

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

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

39 cutaneous melanoma data set showed that high GILT mRNA expression was associated with improved overal

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

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

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

43 ducible cellular proteins, including IFITMs, GILT, ADAP2, 25CH, and LY6E, had been identified to modu

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

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

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

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

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

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

50 ssing and presentation components, including GILT.

51 1 plays a direct role in IFN-gamma-inducible GILT expression.

52 These cytokines were capable of inducing GILT expression in human melanoma cells in vitro.

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

54 Only chimeras that lacked GILT in both TECs and hematopoietic cells had a high con

55 Mice lacking GILT are deficient in generating major histocompatibilit

56 -interferon responsive lysosomal thiol-like (GILT-like) has an anti-ZIKV effect, adenosine deaminase

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

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

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

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

61 not expressed in benign melanocytes of nevi, GILT and MHC class II expression is induced in malignant

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

63 led that ectopic expression of LY6E, but not GILT or ADAP2, in HEK 293 cells inhibited the entry of H

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

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

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

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

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

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

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

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

72 ed stronger responsiveness in the absence of GILT.

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

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

75 n, and is consistent with the association of GILT expression with improved survival in melanoma.

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

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

78 ecursor GILT and decreases the efficiency of GILT maturation.

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

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

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

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

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

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

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

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

87 To explore potential mechanisms of GILT's association with patient outcome, we investigated

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

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

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

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

92 The role of GILT in thymic Ag processing and generation of central t

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

117 N-gamma-inducible lysosomal thiol reductase (GILT) is critical for MHC class II-restricted presentati

118 mma-IFN-inducible lysosomal thiol reductase (GILT) is critical for MHC class II-restricted presentati

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

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

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

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

123 n-gamma-inducible lysosomal thiol reductase (GILT), CD74 and ARFGAP with dual pleckstrin homology dom

124 feron-y-inducible lysosomal thiol reductase (GILT), CD74 and ARFGAP with dual pleckstrin homology dom

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

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

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

128 erferon-inducible lysosomal thiol reductase (GILT).

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

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

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

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

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

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

135 We found that GILT enhanced the negative selection of TRP1-specific th

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

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

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

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

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

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

142 lysosome/endosome-localized thiolreductase (GILT), and lymphocyte antigen 6 family member E (LY6E),

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

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

145 Thus, GILT expression in thymic APCs, and mTECs in particular,

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

147 outcome, we investigated pathways related to GILT function and expression.

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

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

150 and IL-1beta was positively associated with GILT expression in melanoma specimens.

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