ライフサイエンスコーパス: LAIR-1

1 LAIR-1 is a 32 kDa transmembrane glycoprotein with a sin

2 LAIR-1 is hyper-phosphorylated on tyrosyl residues in ce

3 LAIR-1 recruits SHP-1 and SHP-2 phosphatases upon activa

4 LAIR-1(-/-) mice have lower serum levels of IgG1 and, in

5 and leukocyte-associated Ig-like receptor 1 (LAIR-1; CD305), an inhibitory receptor expressed on hema

6 tor leukocyte-associated Ig-like receptor-1 (LAIR-1) in vitro delivers an inhibitory signal that is a

7 Leukocyte associated Ig-like receptor-1 (LAIR-1) is a surface molecule expressed on human mononuc

8 to leukocyte-associated Ig-like receptor-1 (LAIR-1), a recently cloned transmembrane protein.

9 e-associated immunoglobulin-like receptor-1 (LAIR-1), that is constitutively expressed on the majorit

10 e-associated immunoglobulin-like receptor-1 (LAIR-1).

11 led leukocyte-associated Ig-like receptor-1 (LAIR-1).

12 Because LAIR-1(+/+) and LAIR-1(-/-) T cells traffic with equal proficiency to pe

13 ferences in the responses of LAIR-1(-/-) and LAIR-1(+/+) mice were observed.

14 receptors, glycoprotein VI, alpha2beta1, and LAIR-1, determines a decrease in MK migration due to the

15 Whole C1q is required to crosslink CD33 and LAIR-1 and concurrently activate CD33/LAIR-1 inhibitory

16 ecause C1q contains collagen-like motifs and LAIR-1 is a universal collagen receptor, we hypothesized

17 is mediated through a complex with RAGE and LAIR-1 and depends on relative levels of C1q and HMGB1.

18 e intracellular signals when ligated by anti-LAIR-1 mAb, but only LAIR-1 wt cells respond to collagen

19 "effector" T cells, can be inhibited by anti-LAIR-1 mAb.

20 As LAIR-1(-/-) mice age, the splenic T cell population show

21 Because LAIR-1(+/+) and LAIR-1(-/-) T cells traffic with equal p

22 Both LAIR-1 wt and R65K cells can generate intracellular sign

23 bition of DC differentiation was reversed by LAIR-1 siRNA.

24 33 and LAIR-1 and concurrently activate CD33/LAIR-1 inhibitory motifs.

25 sting further biological control of C1q-CD33/LAIR-1 processes.

26 r C1q binds to CD33 and if C1q mediates CD33/LAIR-1 crosslinking.

27 SF, but not DC growth factors, sustains CD33/LAIR-1 expression on both healthy and SLE cells suggesti

28 nsistent with defective self-tolerance, CD33/LAIR-1 expression is reduced in systemic lupus erythemat

29 with LAIR-1 wild-type (wt)-expressing cells, LAIR-1 R65K cells show markedly reduced binding to colla

30 In addition to NK cells, LAIR-1 is expressed on T cells, B cells, macrophages, an

31 showed that, under physiological conditions, LAIR-1 links more closely to the common genes in mouse t

32 s other than that of the broadly distributed LAIR-1/p40 molecule.

33 Finally, B6.DR1/LAIR-1(-/-) and B6.DR1/LAIR-1(+/+) mice were challenged for CIA and mean severi

34 Finally, B6.DR1/LAIR-1(-/-) and B6.DR1/LAIR-1(+/+) mice were challenged

35 ing LAIR-1 Abs suppresses CIA whereas B6.DR1/LAIR-1(-/-) mice develop more severe arthritis than wild

36 When B6.DR1/LAIR-1(-/-) mice were immunized with type II collagen th

37 Thus, C1q is a functional ligand for LAIR-1 restricting immune cell differentiation and activ

38 thesized that C1q is a functional ligand for LAIR-1.

39 the in vivo function of LAIR-1, we generated LAIR-1(-/-) mice.

40 urs, implying that the species difference in LAIR-1 genetic pathways could not be primarily attribute

41 urified CD4(+) cells that were sufficient in LAIR-1, CD3-induced cytokine secretion was significantly

42 , this study opens the door for insight into LAIR-1 functions inside the human body, and raises conce

43 Like LAIR-1, CD33 inhibitory immunoreceptors are highly expre

44 Likewise, LAIR-1 R65K protein has decreased avidity for cells expr

45 ing protein of SHP-1 on the plasma membrane, LAIR-1 may play an important role in hematopoietic cell

46 cell cytokine response through the action of LAIR-1.

47 that defective expression or dysfunction of LAIR-1, a novel immunoinhibitory receptor for collagen,

48 colitis, were used to examine the effect of LAIR-1 deficiency, and no differences in the responses o

49 express two biochemically distinct forms of LAIR-1, which we now show are likely alternative splice

50 To study the in vivo function of LAIR-1, we generated LAIR-1(-/-) mice.

51 ic mice were used to study the importance of LAIR-1 in autoimmune arthritis.

52 1 and LAIR-2 (CD306), a soluble inhibitor of LAIR-1.

53 e, Arg65, is critical for the interaction of LAIR-1 with collagens.

54 er, we found that the in vivo interaction of LAIR-1 with LAIR-2 rarely occurs, implying that the spec

55 en, which correlates with a reduced level of LAIR-1 polarization to the site of interaction with coll

56 Cross-linking of LAIR-1 on human T cell clones results in inhibition of c

57 responsible for tyrosine phosphorylation of LAIR-1 and recruitment of SHP-1.

58 its collagen tail trigger phosphorylation of LAIR-1 immunoreceptor tyrosine-based inhibitory motifs (

59 responsible for tyrosine phosphorylation of LAIR-1 may belong to the Src family since PP1, a Src fam

60 ency, and no differences in the responses of LAIR-1(-/-) and LAIR-1(+/+) mice were observed.

61 experimental data in relation to the role of LAIR-1 immune regulation may be overestimated when appli

62 We analyzed the variation of LAIR-1 genetic pathways in murine versus human internal

63 he effect of a conservative R65K mutation on LAIR-1 ligand binding and function.

64 ls when ligated by anti-LAIR-1 mAb, but only LAIR-1 wt cells respond to collagens or matrigel.

65 Splenocytes from wild-type or LAIR-1(-/-) mice were stimulated with soluble anti-CD3 A

66 Tyrosine-phosphorylated LAIR-1 specifically interacts with SHP-1 but not with SH

67 Like engagement of the ITIM-bearing receptor LAIR-1/p40, cross-linking of FDF03 inhibited calcium mob

68 d to human killer cell inhibitory receptors, LAIR-1 does not appear to recognize human leukocyte anti

69 Treatment with stimulating LAIR-1 Abs suppresses CIA whereas B6.DR1/LAIR-1(-/-) mic

70 n together, these observations indicate that LAIR-1 plays a role in regulating immune cells and sugge

71 This indicates that LAIR-1 provides a mechanism of regulation of effector T

72 rface plasmon resonance analyses showed that LAIR-1 R65K protein has markedly reduced avidity for col

73 These data suggest that LAIR-1 may be a potential therapeutic target for suppres

74 ike region (CLR) engaging and activating the LAIR-1 inhibitory immunoreceptor represents a non-comple

75 es upon activation, and cross-linking of the LAIR-1 antigen on natural killer (NK) cells results in s

76 Thus, LAIR-1 functions as an inhibitory receptor not only on N

77 exhaustion or inhibition (PD-1, LAG-3, TIM3, LAIR-1, and CTLA-4) and HBV-specific T cells.

78 However, in contrast to LAIR-1/p40, cross-linking of FDF03 did not inhibit GM-CS

79 Treatment with a stimulatory mAb to LAIR-1 also significantly attenuated CIA in the LAIR(+/+

80 e treated with either the stimulatory mAb to LAIR-1 or a hamster IgG control.

81 pressed in the presence of collagen, whereas LAIR-1-deficient splenocytes had no attenuation.

82 hat C1q and its collagen tail associate with LAIR-1 and LAIR-2 (CD306), a soluble inhibitor of LAIR-1

83 Compared with LAIR-1 wild-type (wt)-expressing cells, LAIR-1 R65K cell

84 ed avidity for collagen type I compared with LAIR-1 wt.

85 The discovery of C1q interactions with LAIR-1 and LAIR-2 lends much needed insight into molecul