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@ARTICLE{Lu:127037,
      author       = {K.-H. Lu$^*$ and S. Keppler and F. Leithäuser and T.
                      Mattfeldt and A. Castello and U. Kostezka and G.
                      Küblbeck$^*$ and S. Schmitt$^*$ and A. Klevenz$^*$ and S.
                      Prokosch$^*$ and G. Pougialis$^*$ and T. Pawson and F.
                      Batista and A. Tafuri$^*$ and B. Arnold$^*$},
      title        = {{N}ck adaptor proteins modulate differentiation and
                      effector function of {T} cells.},
      journal      = {Journal of leukocyte biology},
      volume       = {98},
      number       = {3},
      issn         = {0741-5400},
      address      = {Bethesda, Md.},
      publisher    = {Soc. for Leukocyte Biology},
      reportid     = {DKFZ-2017-03063},
      pages        = {301 - 311},
      year         = {2015},
      abstract     = {Understanding the molecular mechanisms regulating T cell
                      reactivity is required for successful reprogramming of
                      immune responses in medical conditions, characterized by
                      dysfunctions of the immune system. Nck proteins are
                      cytoplasmic adaptors mediating diverse cellular functions,
                      including TCR signaling. By enhancing TCR signal strength,
                      Nck proteins influence thymic selection and regulate the
                      size and sensitivity of the peripheral T cell repertoire.
                      Here, we investigated the contribution of Nck proteins to
                      CD4(+) T cell differentiation and effector function using
                      Nck.T(-/-) mice. Impaired GC formation and reduced Tfh were
                      observed in Nck.T(-/-) mice after immunization with T
                      cell-dependent antigens. Th2/Tfh-related cytokines, such as
                      IL-4, IL-10, and IL-21, were decreased in Nck.T(-/-) mice T
                      cells. Moreover, an increased susceptibility to cell death
                      of Tfh cells in Nck.T(-/-) mice was associated with
                      decreased levels of Akt phosphorylation. As a result of this
                      dysregulation in Tfh cells of Nck.T(-/-) mice, we found
                      impaired production and affinity maturation of antibodies
                      against T cell-dependent antigens. Thus, Nck proteins not
                      only participate in thymic selection and generation of the
                      peripheral T cell repertoire but also are involved in the
                      differentiation and effector functions of CD4(+) T cells.},
      keywords     = {Adaptor Proteins, Signal Transducing (NLM Chemicals) /
                      Cytokines (NLM Chemicals) / Nck protein (NLM Chemicals) /
                      Oncogene Proteins (NLM Chemicals) / Transcription Factors
                      (NLM Chemicals)},
      cin          = {D050},
      ddc          = {610},
      cid          = {I:(DE-He78)D050-20160331},
      pnm          = {314 - Tumor immunology (POF3-314)},
      pid          = {G:(DE-HGF)POF3-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:25995205},
      doi          = {10.1189/jlb.1HI1114-565R},
      url          = {https://inrepo02.dkfz.de/record/127037},
}