ライフサイエンスコーパス: scurfy

1 Both scurfy and normal T cells are responsive to two distinct

2 Transfer of Scurfy CD4(+) T cells into nu/nu mice yielded autoantibo

3 a T cells in the TCRalpha(-/-) recipients of scurfy cells markedly expanded and expressed a highly ac

4 provided by the TCR and by ligation of CD28; scurfy cells, however, are hyperresponsive to TCR ligati

5 Furthermore, complementation of Foxp3 in scurfy-derived T cells lowers the NFAT and NF-kappa B tr

6 In addition, development of the Scurfy disease also may require mutation of the gene in

7 reproduces the inflammatory phenotype of the scurfy donor, including hepatitis and pneumonitis.

8 tute immunodeficient mice in the presence of scurfy fetal liver cells.

9 In mixed chimeras with Scurfy fetal liver, Tregs derived from IFNAR KO bone mar

10 Scurfy (Foxp3(Sf)/Y), Il2(-/-), and Il2ralpha(-/-) mice

11 eous diabetes onset, since crossing onto the scurfy (Foxp3) mutation, BDC12-4.1 TCR Tg mice develop a

12 cell transfers, we tested the effect of the scurfy loss-of-function mutation of the Foxp3 gene in th

13 injury, we co-transferred isolated Tregs and Scurfy lymph node cells; Treg repletion significantly at

14 Transfer of scurfy lymphocytes to RAG deficient (RAG(-/-)) recipient

15 is and pneumonitis in RAG(-/-) recipients of scurfy lymphocytes.

16 dermatitis, induced by adoptive transfer of scurfy lymphocytes.

17 Consistent with this, T cells from Scurfy mice (FoxP3 mutant) lacked HVEM gene expression,

18 e FOXP3, the ortholog of the gene mutated in scurfy mice (Foxp3), causes IPEX syndrome.

19 uman ortholog (FOXP3) of the gene mutated in scurfy mice (Foxp3), in IPEX patients.

20 Mutation of Foxp3 in Scurfy mice and FOXP3 in humans with IPEX results in fat

21 autoimmune syndrome observed in Foxp3-mutant scurfy mice and Foxp3-null mice results from a CD4+CD25+

22 oimmune disease affecting multiple organs in Scurfy mice and humans with the immune dysregulation, po

23 e severity of the autoimmune diseases in the scurfy mice and in patients who have immunodysregulation

24 ells and massive multi-organ autoimmunity in scurfy mice and IPEX (immune dysregulation, polyendocrin

25 of our study indicate that autoantibodies in Scurfy mice and patients with IPEX target keratins.

26 tions substantially improved the survival of scurfy mice by blocking effector T-cell differentiation.

27 the etiology of lethal autoimmune disease in scurfy mice by stimulating the differentiation of antige

28 inatal period, germline mutation of FoxP3 in scurfy mice caused lymphopenia in the spleen and massive

29 In this study, we show that Scurfy mice develop autoantibodies directed against skin

30 During the course of disease, Scurfy mice develop autoantibodies; however, the targete

31 Scurfy mice develop CD4 T-cell-mediated lymphoproliferat

32 port that removal of CD28 expression rescued scurfy mice from early death.

33 we show that Foxp3-deficient T(reg) cells in scurfy mice harboring a null mutation of the Foxp3 gene

34 Scurfy mice have a deletion in the Foxp3 gene, resulting

35 More importantly, T cells derived from scurfy mice have a dramatic increase in nuclear factor o

36 cells from wild-type mice or FoxP3-deficient Scurfy mice into T cell- and B cell-deficient RAG-1 knoc

37 Longer-term surviving CD28-deficient scurfy mice still had lymphoproliferative disorder, but

38 We used DEREG and Scurfy mice to assess the role of Foxp3(+) regulatory T

39 he T reg cell compartment in Foxp3-deficient scurfy mice with cells whose ability to migrate to the s

40 rrying a loss-of-function mutation in FoxP3 (scurfy mice) present with fatal autoimmune-like disease

41 We found that in mice deficient in Foxp3 (scurfy mice), a model of autoimmunity, the development o

42 5) knockout (KO) mice but not in IL-2 KO and scurfy mice, although all three mutants lack regulatory

43 p3 as the gene responsible for the defect in scurfy mice, and subsequently, the demonstration of its

44 ssive autoimmune syndrome similar to that of scurfy mice, but does not affect thymic development, hom

45 expansion of pathogenic T cells derived from scurfy mice, failed to mediate T follicular regulatory c

46 In most patients with IPEX and also in scurfy mice, T cells show hyperreactivity and levels of

47 Scurfy mice, which are deficient in a functional Foxp3,

48 ) and a fatal systemic autoimmune disease in scurfy mice.

49 e or Treg-depleted CD4 T cells in curing the scurfy mice.

50 Although Foxp3-deficient (Scurfy) mice lacked Treg cells, they contained Triple(hi

51 CD4(+) T cell isolated from a Treg-deficient scurfy mouse.

52 ting lymphoproliferation and autoimmunity in scurfy mutant mice and immunodysregulation polyendocrino

53 of Foxp3 caused severe autoimmune disease in scurfy mutant mice, the other functional domains of Foxp

54 The scurfy mutation causes loss of function of the foxp3 gen

55 The Scurfy mutation of the FoxP3 gene (FoxP3(sf)) in the mou

56 onfirmed, as the signals were ablated by the Scurfy mutation of the FoxP3 gene.

57 pretation of our data would suggest that the scurfy mutation results in a defect, which interferes wi

58 e diabetogenic cascade, we crossed the Foxp3 scurfy mutation, which eliminates T reg cells, with the

59 d Foxp3, the gene defective in mice with the scurfy mutation.

60 Mutation of the Foxp3 gene causes the scurfy phenotype in mouse and IPEX syndrome (immune dysf

61 Most of the Scurfy sera tested identified a major band at 50 kDa.

62 Scurfy serum predominantly recognized the C-terminal fra

63 Using western blot analysis, we found that Scurfy serum reacted with proteins in total skin lysate,

64 imal mouse X chromosome containing the mouse scurfy (sf) and tattered (Td) mutations.

65 hemizygous (Xsf/Y) for the X-linked mutation scurfy (sf) develop a severe and rapidly fatal lymphopro

66 Scurfy (sf) is an X-linked recessive mouse mutant result

67 (OVA-specific, Vbeta5(high)Valpha2(high)) Tg scurfy (Sf) mice (OT-II Sf) that lack Treg, nonclonotypi

68 Scurfy (Sf) mice bear a mutation in the Foxp3 transcript

69 Scurfy (Sf) mice lack CD4(+)Foxp3(+) regulatory T cells

70 utation of the Foxp3 transcription factor in Scurfy (Sf) mice results in complete absence of the CD4+

71 Therefore, we examined Scurfy (Sf) mice, animals that have a mutation in the ge

72 tion on autoimmune inflammation, we examined scurfy (Sf) mice, which are deficient in Tregs and succu

73 vation and autoimmune pathology in Foxp3(-/-)Scurfy (sf) mice.

74 MIM 304930) is the genetic equivalent of the scurfy (sf) mouse, we sequenced the human ortholog (FOXP

75 biosis and autoimmunity over the lifespan of scurfy (SF) mouse.

76 he Rag2(-/-) and the Rag2(-/-) mice with the Scurfy (sf) mutation (FoxP3(sf/Y) or FoxP3(sf/sf)) to ev

77 tudy, we investigated the reason that SMG of Scurfy (Sf), Sf.Il2(-/-), Sf.Il2ralpha(-/-), and the lon

78 ses of lymphoid cell populations reveal that scurfy syndrome is characterized by changes in several p

79 Scurfy T cells also exhibit strong up-regulation of cell

80 ot been identified, we also demonstrate that scurfy T cells are less sensitive than normal controls t

81 A high frequency of scurfy T cells in TCRalpha(-/-) recipients produced IL-1

82 enhance suppressor cytokine production from scurfy T cells in TCRalpha(-/-) recipients.

83 nd B7-2, whose expression is up-regulated on scurfy T cells.

84 f the cytokine granulocyte-macrophage CSF by scurfy T cells.

85 super> T cells infiltrated the skin, whereas Scurfy Triple(lo)CD4(+) T cells induced colitis and wast