DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming

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

doi:https://doi.org/10.1016/S1074-7613(00)00034-0

DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming

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

Research output: Contribution to journal › Article › Academic › peer-review

204 Citations (Scopus)

Abstract

DAP12 is an ITAM-bearing membrane adaptor molecule implicated in the activation of NK and myeloid cells. In mice rendered DAP12 deficient by targeted gene disruption, lymphoid and myeloid development was apparently normal, although the activating Ly49 receptors on NK cells were downregulated and nonfunctional. To analyze the consequences of DAP12 deficiency in vivo, we examined the susceptibility of DAP12(-/-) mice to experimental autoimmune encephalomyelitis (EAE). DAP12(-/-) mice were resistant to EAE induced by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide. Resistance was associated with a strongly diminished production of IFNγ by myelin-reactive CD4⁺ T cells due to inadequate T cell priming in vivo. These data suggest that DAP12 signaling may be required for optimal antigen-presenting cell (APC) function or inflammation.

Original language	English
Pages (from-to)	345-353
Number of pages	9
Journal	Immunity
Volume	13
Issue number	3
DOIs	https://doi.org/10.1016/S1074-7613(00)00034-0
Publication status	Published - 2000

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@article{ae78676537d94200a336b80df1c0f890,

title = "DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming",

abstract = "DAP12 is an ITAM-bearing membrane adaptor molecule implicated in the activation of NK and myeloid cells. In mice rendered DAP12 deficient by targeted gene disruption, lymphoid and myeloid development was apparently normal, although the activating Ly49 receptors on NK cells were downregulated and nonfunctional. To analyze the consequences of DAP12 deficiency in vivo, we examined the susceptibility of DAP12(-/-) mice to experimental autoimmune encephalomyelitis (EAE). DAP12(-/-) mice were resistant to EAE induced by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide. Resistance was associated with a strongly diminished production of IFNγ by myelin-reactive CD4+ T cells due to inadequate T cell priming in vivo. These data suggest that DAP12 signaling may be required for optimal antigen-presenting cell (APC) function or inflammation.",

author = "Bakker, {Alexander B.H.} and Hoek, {Robert M.} and Adelheid Cerwenka and Bianca Blom and Linda Lucian and Tom McNeil and Richard Murray and Phillips, {Joseph H.} and Sedgwick, {Jonathon D.} and Lanier, {Lewis L.}",

note = "Funding Information: We thank Dr. A. Kane (Brown University, Providence, RI) for her gift of the AK7 and AK40 cells and Drs. H. Smith, and W. Yokoyama for generously providing mAbs. We acknowledge Drs. A. Beebe, B. Homey, and D. Cua for help with animal experiments; M. Bigler for cell culture; and J. Katheiser, G. Burget, and M. Andonian for graphics. Schering Plough Corporation supports the DNAX Research Institute. The Sandler Family Supporting Foundation partially funded studies at UCSF.",

year = "2000",

doi = "https://doi.org/10.1016/S1074-7613(00)00034-0",

language = "English",

volume = "13",

pages = "345--353",

journal = "Immunity",

issn = "1074-7613",

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number = "3",

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T1 - DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming

AU - Bakker, Alexander B.H.

AU - Hoek, Robert M.

AU - Cerwenka, Adelheid

AU - Blom, Bianca

AU - Lucian, Linda

AU - McNeil, Tom

AU - Murray, Richard

AU - Phillips, Joseph H.

AU - Sedgwick, Jonathon D.

AU - Lanier, Lewis L.

N1 - Funding Information: We thank Dr. A. Kane (Brown University, Providence, RI) for her gift of the AK7 and AK40 cells and Drs. H. Smith, and W. Yokoyama for generously providing mAbs. We acknowledge Drs. A. Beebe, B. Homey, and D. Cua for help with animal experiments; M. Bigler for cell culture; and J. Katheiser, G. Burget, and M. Andonian for graphics. Schering Plough Corporation supports the DNAX Research Institute. The Sandler Family Supporting Foundation partially funded studies at UCSF.

PY - 2000

Y1 - 2000

N2 - DAP12 is an ITAM-bearing membrane adaptor molecule implicated in the activation of NK and myeloid cells. In mice rendered DAP12 deficient by targeted gene disruption, lymphoid and myeloid development was apparently normal, although the activating Ly49 receptors on NK cells were downregulated and nonfunctional. To analyze the consequences of DAP12 deficiency in vivo, we examined the susceptibility of DAP12(-/-) mice to experimental autoimmune encephalomyelitis (EAE). DAP12(-/-) mice were resistant to EAE induced by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide. Resistance was associated with a strongly diminished production of IFNγ by myelin-reactive CD4+ T cells due to inadequate T cell priming in vivo. These data suggest that DAP12 signaling may be required for optimal antigen-presenting cell (APC) function or inflammation.

AB - DAP12 is an ITAM-bearing membrane adaptor molecule implicated in the activation of NK and myeloid cells. In mice rendered DAP12 deficient by targeted gene disruption, lymphoid and myeloid development was apparently normal, although the activating Ly49 receptors on NK cells were downregulated and nonfunctional. To analyze the consequences of DAP12 deficiency in vivo, we examined the susceptibility of DAP12(-/-) mice to experimental autoimmune encephalomyelitis (EAE). DAP12(-/-) mice were resistant to EAE induced by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide. Resistance was associated with a strongly diminished production of IFNγ by myelin-reactive CD4+ T cells due to inadequate T cell priming in vivo. These data suggest that DAP12 signaling may be required for optimal antigen-presenting cell (APC) function or inflammation.

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U2 - https://doi.org/10.1016/S1074-7613(00)00034-0

DO - https://doi.org/10.1016/S1074-7613(00)00034-0

M3 - Article

C2 - 11021532

SN - 1074-7613

VL - 13

SP - 345

EP - 353

JO - Immunity

JF - Immunity

IS - 3

ER -

DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming

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