Journal Article

DKFZ-2017-03063

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Nck adaptor proteins modulate differentiation and effector function of T cells.

Lu, K.-H.DKFZ* ; Keppler, S. ; Leithäuser, F. ; Mattfeldt, T. ; Castello, A. ; Kostezka, U. ; Küblbeck, G.DKFZ* ; Schmitt, S.DKFZ* ; Klevenz, A.DKFZ* ; Prokosch, S.DKFZ* ; Pougialis, G.DKFZ* ; Pawson, T. ; Batista, F. ; Tafuri, A.DKFZ* ; Arnold, B. (Last author)DKFZ*

2015
Soc. for Leukocyte Biology Bethesda, Md.

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Please use a persistent id in citations: doi:10.1189/jlb.1HI1114-565R

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.

Keyword(s): Adaptor Proteins, Signal Transducing ; Cytokines ; Nck protein ; Oncogene Proteins ; Transcription Factors

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Contributing Institute(s):

1. Molekulare Immunologie (D050)

Research Program(s):

1. 314 - Tumor immunology (POF3-314) (POF3-314)

Appears in the scientific report 2015

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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