title: Reduction of CRKL expression in patients with partial DiGeorge syndrome is associated with impairment of T-cell functions.
abstract: 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 1α, 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.
  
  
  
  We aimed to investigate the role of CRKL in T-cell functional responses in patients affected with pDGS.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pediatrics, Institute of Molecular Medicine "Angelo Nocivelli", University of Brescia, Brescia, Italy; Scuola di Dottorato in Scienze della Riproduzione e dello Sviluppo, University of Trieste, Trieste, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Giacomelli
authors.affiliation: Department of Pediatrics, Institute of Molecular Medicine "Angelo Nocivelli", University of Brescia, Brescia, Italy; Scuola di Dottorato in Scienze della Riproduzione e dello Sviluppo, University of Trieste, Trieste, Italy.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Pediatrics, Institute of Molecular Medicine "Angelo Nocivelli", University of Brescia, Brescia, Italy.
authors.forename: Annarosa
authors.initials: A
authors.lastname: Soresina
authors.affiliation: Pathology Department, University of Verona, Verona, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Tamassia
authors.affiliation: Department of Pediatrics, Institute of Molecular Medicine "Angelo Nocivelli", University of Brescia, Brescia, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Lorenzini
authors.affiliation: Department of Pediatrics, Institute of Molecular Medicine "Angelo Nocivelli", University of Brescia, Brescia, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Moratto
authors.affiliation: Pathology Department, University of Verona, Verona, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Gasperini
authors.affiliation: Pathology Department, University of Verona, Verona, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Cassatella
authors.affiliation: Department of Pediatrics, Institute of Molecular Medicine "Angelo Nocivelli", University of Brescia, Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.affiliation: Department of Pediatrics, Institute of Molecular Medicine "Angelo Nocivelli", University of Brescia, Brescia, Italy.
authors.forename: Vassilios
authors.initials: V
authors.lastname: Lougaris
authors.affiliation: Department of Pediatrics, Institute of Molecular Medicine "Angelo Nocivelli", University of Brescia, Brescia, Italy. Electronic address: raffaele.badolato@unibs.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Badolato
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D016022:Case-Control Studies; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis; D004062:DiGeorge Syndrome / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000276:immunology; D007223:Infant; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D034622:RNA Interference; D050799:STAT5 Transcription Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; C082869:CRKL protein; D016207:Cytokines; D007132:Immunoglobulin Isotypes; D009687:Nuclear Proteins; D050799:STAT5 Transcription Factor
keywords: CRKL; DiGeorge syndrome; IL-2; T-cell receptor activation; c-Fos; proliferation; signal transducer and activator of transcription 5