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.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 assaysin vitroand 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,CRKLsilencing 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.