DAP12-Deficient Mice Fail to Develop Autoimmunity Due to Impaired Antigen Priming

Bakker, Alexander B. H.; Hoek, Robert M.; Cerwenka, Adelheid; Blom, Bianca; Lucian, Linda; McNeil, Tom; Murray, Richard M.; Phillips, Joseph H.; Sedgwick, Jonathon D.; Lanier, Lewis L.

doi:10.1016/s1074-7613(00)00034-0

Cited by 215 publications

(179 citation statements)

References 45 publications

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“…We used offspring of DAP12 ϩ/Ϫ FcR␥ Ϫ/Ϫ ϫ DAP12 Ϫ/Ϫ FcR␥ ϩ/Ϫ matings (B6͞129 mixed background) derived from intercrossing DAP12 Ϫ/Ϫ (12) and FcR␥ Ϫ/Ϫ (Taconic Farms) mice. Heterozygous animals were considered wild type given no suggestion of gene dosage effects for DAP12 or FcR␥ in prior analyses.…”

Section: Methodsmentioning

confidence: 99%

The immunomodulatory adapter proteins DAP12 and Fc receptor γ-chain (FcRγ) regulate development of functional osteoclasts through the Syk tyrosine kinase

Mócsai

Humphrey²,

Ziffle³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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438

446

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Section: Methodsmentioning

confidence: 99%

The immunomodulatory adapter proteins DAP12 and Fc receptor γ-chain (FcRγ) regulate development of functional osteoclasts through the Syk tyrosine kinase

Mócsai

Humphrey²,

Ziffle³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

438

446

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“…RAE-1ε transgenic mice were generated as described previously and were backcrossed onto the C57BL/6 background 33 . DAP12-deficient mice on the C57BL/6 background (backcrossed 9 generation) were described previously 34 , and DAP10-deficient mice were generated from C57BL/6 embryonic stem cells (JHP, unpublished). All experiments were performed according to the guidelines of the UCSF Committee on Animal Research and the Schering Plough BioPharma Committee on Animal Research.…”

Section: Methods Micementioning

confidence: 99%

Function of NKG2D in natural killer cell–mediated rejection of mouse bone marrow grafts

et al. 2005

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Irradiation-resistant NK cells in a F1 recipient can reject parental bone marrow (BM), and host NK cells can also prevent engraftment of allogeneic BM. We show that repopulating BM cells in certain mouse strains express the RAE-1 proteins, which are ligands for the activating NKG2D NK cell receptor. Treatment with a neutralizing NKG2D antibody prevented rejection of parental BALB/c BM in (C57BL/6 × BALB/c) F1 recipients, and allowed engraftment of allogeneic BALB.B BM in C57BL/6 recipients. Additionally, BM from RAE-1ε transgenic C57BL/6 mice was rejected by syngeneic animals, but accepted with anti-NKG2D treatment. If other stem cells or tissues upregulate expression of NKG2D ligands after transplantation, NKG2D may contribute to graft rejection in immunocompetent hosts.Natural killer (NK) cells play a critical role in the elimination of virus-infected cells or transformed cells 1 . Although beneficial in host protection against infectious disease and cancer, irradiation-resistant mouse NK cells can reject bone marrow (BM) cell grafts 2 -5 . This process whereby NK cells in F1 recipients reject parental BM grafts has been called F1 hybrid resistance 6 , 7 . Initially, the hypothesis proposed to explain hybrid resistance was the expression of hybrid histocompatibility (Hh) antigens on parental bone marrow cells that were not expressed in the F1 hybrid mice. Genetic mapping studies suggested that at least in some mouse strains the genes regulating the Hh antigens localized to the H-2S/D region 8 . More recently, the ability of NK cells to recognize and reject parental BM cells has been explained, in part, by the lack of inhibitory Ly49 receptors specific for parental H-2 proteins on a subset of NK cells in the F1 recipient 9 -12 . Thus, a subset of NK cells in the F1 recipient lacking inhibitory receptors for the parental BM cells might eliminate these parental BM grafts. However, the NK cell receptors that initiate the attack against BM grafts have not been defined.NKG2D is an activating receptor that is expressed on the cell surface of NK cells, activated CD8 + T cells and γδTcR + T cells 13 . In resting NK cells, NKG2D associates with the DAP10 adapter protein, and in activated mouse NK cells an NKG2D isoform generated by alternative splicing can also associate with the DAP12 adapter protein 14 . NKG2D binds to a family of ligands with structural homology to major histocompatibility complex (MHC) class I proteins 1 , 15 ). In mice, the retinoic acid early inducible-1 (RAE-1) family of proteins, H60 and MULT1 function as high affinity ligands for NKG2D 16 -18 . Although the genes encoding the RAE-1 proteins were first discovered by their expression in embryonic tissues 19 , 20 , they are largely silent in normal, healthy tissues in adult mice, but are induced by viral infection or cellular transformation. Here, we have examined expression of the NKG2D ligands in BM cells repopulating irradiated mice and have evaluated the role of NKG2D in hybrid resistance. RESULTS Expression of NKG2D ligands on ...

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“…only develop osteopetrosis 20,60,61 but also are resistant to EAE. 62 Interestingly, genetic mutations in human DAP12 or TREM-2 result in a bone-fracture syndrome called Nasu-Hakola disease, further suggesting that plexin-A1 physiologically associates with the TREM/ DAP12 complex and that this interaction is relevant to these diseases.…”

Section: Regulation Of Immune Cell Responses H Takamatsu Et Al 85mentioning

confidence: 99%

Regulation of immune cell responses by semaphorins and their receptors

2010

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Semaphorins were originally identified as axon guidance factors involved in the development of the neuronal system. However, accumulating evidence indicates that several members of semaphorins, so-called 'immune semaphorins', are crucially involved in various phases of immune responses. These semaphorins regulate both immune cell interactions and immune cell trafficking during physiological and pathological immune responses. Here, we review the following two functional aspects of semaphorins and their receptors in immune responses: their functions in cell-cell interactions and their involvement in immune cell trafficking.

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DAP12-Deficient Mice Fail to Develop Autoimmunity Due to Impaired Antigen Priming

Cited by 215 publications

References 45 publications

The immunomodulatory adapter proteins DAP12 and Fc receptor γ-chain (FcRγ) regulate development of functional osteoclasts through the Syk tyrosine kinase

The immunomodulatory adapter proteins DAP12 and Fc receptor γ-chain (FcRγ) regulate development of functional osteoclasts through the Syk tyrosine kinase

Function of NKG2D in natural killer cell–mediated rejection of mouse bone marrow grafts

Regulation of immune cell responses by semaphorins and their receptors

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