Correction: A novel human IL2RB mutation results in T and NK cell–driven immune dysregulation

JOURNAL OF EXPERIMENTAL MEDICINE(2019)

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摘要
The pleiotropic actions of interleukin-2 (IL-2) are essential for regulation of immune responses and maintenance of immune tolerance. The IL-2 receptor (IL-2R) is composed of IL-2R alpha, IL-2R beta, and IL-2R gamma subunits, with defects in IL-2R alpha and IL-2R gamma and their downstream signaling effectors resulting in known primary immunodeficiency disorders. Here, we report the first human defect in IL-2R beta, occurring in two infant siblings with a homozygous IL2RB mutation in the WSXWS motif, manifesting as multisystem autoimmunity and susceptibility to CMV infection. The hypomorphic mutation results in diminished IL-2R beta surface expression and dysregulated IL-2/15 signaling, with an anticipated reduction in regulatory T cells. However, in contrast to the IL-2R beta(-/-) animal model, which lacks NK cells, these siblings demonstrate an expansion of NK cells, particularly the CD56(bright) subset, and a lack of terminally differentiated NK cells. Thus, the early-onset autoimmunity and immunodeficiency are linked to functional deficits arising from altered IL-2R beta expression and signaling in T and NK cells.
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