Reduction of CRKL expression in patients with partial DiGeorge syndrome is associated with impairment of T-cell functions

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:138

Article

Giacomelli, Mauro^1,2  Kumar, Rajesh^1,2  Soresina, Annarosa¹  Tamassia, Nicola³  Lorenzini, Tiziana¹  Moratto, Daniele¹  Gasperini, Sara³  Cassatella, Marco³  Plebani, Alessandro¹  Lougaris, Vassilios¹  Badolato, Raffaele¹ 

[1] Univ Brescia, Inst Mol Med Angelo Nocivelli, Dept Pediat, Brescia, Italy

[2] Univ Trieste, Scuola Dottorato Sci Riprod & Sviluppo, Trieste, Italy

[3] Univ Verona, Dept Pathol, Verona, Italy

关键词: CRKL;    DiGeorge syndrome;    c-Fos;    proliferation;    T-cell receptor activation;    IL-2;    signal transducer and activator of transcription 5;   

DOI  :  10.1016/j.jaci.2015.10.051

来源: Elsevier

【 摘 要 】

Background: Partial DiGeorge syndrome (pDGS) is caused by deletion of the 22q11.2 region. Within this region lies CrK-like (CRKL), a gene encoding an adapter protein belonging to the Crk family that is involved in the signaling cascade of IL-2, stromal cell-derived factor 1 alpha, and type I interferon. Although recurrent infections can be observed in patients with deletion of chromosome 22 syndrome, the immune pathogenesis of this condition is yet not fully understood. Objective: We aimed to investigate the role of CRKL in T-cell functional responses in patients affected with pDGS. Methods: Protein expression levels and phosphorylation of CRKL were evaluated in patients with pDGS. T-cell functional assays in vitro and gene-silencing experiments were also performed. Results: CRKL protein expression, as well as its phosphorylation, were reduced in all patients with pDGS, especially on IL-2 stimulation. Moreover, T cells presented impaired proliferation and reduced IL-2 production on anti-CD3/CD28 stimulation and decreased c-Fos expression. Finally, CRKL silencing in Jurkat T cells resulted in impaired T-cell proliferation and reduced c-Fos expression. Conclusions: The impaired T-cell proliferation and reduction of CRKL, phosphorylated CRKL, and c-Fos levels suggest a possible role of CRKL in functional deficiencies of T cells in patients with pDGS.

【 授权许可】

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