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000127037 0247_ $$2doi$$a10.1189/jlb.1HI1114-565R
000127037 0247_ $$2pmid$$apmid:25995205
000127037 0247_ $$2ISSN$$a0741-5400
000127037 0247_ $$2ISSN$$a1938-3673
000127037 037__ $$aDKFZ-2017-03063
000127037 041__ $$aeng
000127037 082__ $$a610
000127037 1001_ $$0P:(DE-HGF)0$$aLu, Kun-Hui$$b0
000127037 245__ $$aNck adaptor proteins modulate differentiation and effector function of T cells.
000127037 260__ $$aBethesda, Md.$$bSoc. for Leukocyte Biology$$c2015
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000127037 520__ $$aUnderstanding the molecular mechanisms regulating T cell reactivity is required for successful reprogramming of immune responses in medical conditions, characterized by dysfunctions of the immune system. Nck proteins are cytoplasmic adaptors mediating diverse cellular functions, including TCR signaling. By enhancing TCR signal strength, Nck proteins influence thymic selection and regulate the size and sensitivity of the peripheral T cell repertoire. Here, we investigated the contribution of Nck proteins to CD4(+) T cell differentiation and effector function using Nck.T(-/-) mice. Impaired GC formation and reduced Tfh were observed in Nck.T(-/-) mice after immunization with T cell-dependent antigens. Th2/Tfh-related cytokines, such as IL-4, IL-10, and IL-21, were decreased in Nck.T(-/-) mice T cells. Moreover, an increased susceptibility to cell death of Tfh cells in Nck.T(-/-) mice was associated with decreased levels of Akt phosphorylation. As a result of this dysregulation in Tfh cells of Nck.T(-/-) mice, we found impaired production and affinity maturation of antibodies against T cell-dependent antigens. Thus, Nck proteins not only participate in thymic selection and generation of the peripheral T cell repertoire but also are involved in the differentiation and effector functions of CD4(+) T cells.
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000127037 650_7 $$2NLM Chemicals$$aAdaptor Proteins, Signal Transducing
000127037 650_7 $$2NLM Chemicals$$aCytokines
000127037 650_7 $$2NLM Chemicals$$aNck protein
000127037 650_7 $$2NLM Chemicals$$aOncogene Proteins
000127037 650_7 $$2NLM Chemicals$$aTranscription Factors
000127037 7001_ $$aKeppler, Selina$$b1
000127037 7001_ $$aLeithäuser, Frank$$b2
000127037 7001_ $$aMattfeldt, Torsten$$b3
000127037 7001_ $$aCastello, Angelo$$b4
000127037 7001_ $$aKostezka, Ulrike$$b5
000127037 7001_ $$0P:(DE-He78)b8759faaf3e907bcd8b6a34983994a3c$$aKüblbeck, Günter$$b6$$udkfz
000127037 7001_ $$0P:(DE-He78)b3374c032cfa377d69c96d357b8a3e50$$aSchmitt, Sabine$$b7$$udkfz
000127037 7001_ $$0P:(DE-He78)de65818249a2e18aa4309f229917f4a4$$aKlevenz, Alexandra$$b8$$udkfz
000127037 7001_ $$0P:(DE-He78)3c6157a315192b4a95e0138399b89da9$$aProkosch, Sandra$$b9$$udkfz
000127037 7001_ $$0P:(DE-He78)534f82cf960a8c8b72ecf7fe702dc42d$$aPougialis, Georg$$b10$$udkfz
000127037 7001_ $$aPawson, Tony$$b11
000127037 7001_ $$aBatista, Facundo$$b12
000127037 7001_ $$0P:(DE-HGF)0$$aTafuri, Anna$$b13
000127037 7001_ $$0P:(DE-He78)554abc2af2666cc3421cc0d7f6e7b6de$$aArnold, Bernd$$b14$$eLast author$$udkfz
000127037 773__ $$0PERI:(DE-600)2026833-6$$a10.1189/jlb.1HI1114-565R$$gVol. 98, no. 3, p. 301 - 311$$n3$$p301 - 311$$tJournal of leukocyte biology$$v98$$x0741-5400$$y2015
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