SH2-domain mutations in STAT3 in hyper-IgE syndrome patients result in impairment of IL-10 function

Eur J Immunol. 2011 Oct;41(10):3075-84. doi: 10.1002/eji.201141721. Epub 2011 Sep 6.


Autosomal-dominant hyper-IgE syndrome (AD-HIES) is a primary immunodeficiency caused by STAT3 mutations. This inherited condition is characterized by eczema, staphylococcal cold abscesses and recurrent pulmonary infections. Given that STAT3 is involved in IL-10 signaling, we examined the immunoregulatory role of IL-10 in inflammation by studying the effects of IL-10 on monocytes, neutrophils and monocyte-derived DCs from HIES subjects. Analysis of gene expression in PBMCs and neutrophils isolated from HIES patients and stimulated with LPS in the presence of IL-10 showed reduced expression of IL1RN, which encodes IL-1 receptor antagonist (IL-1ra), and SOCS3 mRNA but increased CXCL8 mRNA expression. Moreover, secretion of the anti-inflammatory protein IL-1ra was reduced in AD-HIES patients. DCs from HIES patients secreted higher levels of TNF-α, IL-6 and, to a lesser extent, IL-12 when these cells were cultured in the presence of IL-10. These results suggest that IL-10 activity is affected in myeloid cells (e.g. monocytes, DCs) of HIES patients. Impairment of IL-10 signaling in patients with AD-HIES might result in an altered balance between pro-inflammatory and anti-inflammatory signals and might lead to persistent inflammation and delayed healing after infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Dendritic Cells / immunology
  • Female
  • Gene Expression Profiling
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / biosynthesis
  • Interleukin 1 Receptor Antagonist Protein / deficiency
  • Interleukin 1 Receptor Antagonist Protein / genetics
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism*
  • Interleukin-12 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics
  • Job Syndrome / genetics*
  • Job Syndrome / immunology*
  • Lipopolysaccharides / immunology
  • Male
  • Monocytes / immunology
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Neutrophils / immunology
  • Phosphorylation
  • RNA, Messenger / biosynthesis
  • STAT3 Transcription Factor / chemistry
  • STAT3 Transcription Factor / genetics*
  • STAT3 Transcription Factor / metabolism
  • Sequence Analysis, DNA
  • Signal Transduction
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / biosynthesis
  • Suppressor of Cytokine Signaling Proteins / deficiency
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Tumor Necrosis Factor-alpha / biosynthesis
  • src Homology Domains / genetics*


  • CXCL8 protein, human
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-6
  • Interleukin-8
  • Lipopolysaccharides
  • RNA, Messenger
  • SOCS3 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12