Functional Defects in Type 3 Innate Lymphoid Cells and Classical Monocytes in a Patient with Hyper-IgE Syndrome

Yuna Chang; Sung-Yoon Kang; Jihyun Kim; Hye-Ryun Kang; Hye Young Kim

doi:10.4110/in.2017.17.5.352

Functional Defects in Type 3 Innate Lymphoid Cells and Classical Monocytes in a Patient with Hyper-IgE Syndrome

Immune Netw. 2017 Oct;17(5):352-364. doi: 10.4110/in.2017.17.5.352. Epub 2017 Oct 25.

Authors

Yuna Chang^{1

2}, Sung-Yoon Kang^{3

4}, Jihyun Kim^{1

2}, Hye-Ryun Kang^{3

4}, Hye Young Kim^{1

2

4}

Affiliations

¹ Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
² Laboratory of Mucosal Immunology in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
³ Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea.
⁴ Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul 03080, Korea.

Abstract

Hyper-IgE syndrome (HIES) is a very rare primary immune deficiency characterized by elevated serum IgE levels, recurrent bacterial infections, chronic dermatitis, and connective tissue abnormalities. Autosomal dominant (AD) HIES involves a mutation in signal transducer and activator of transcription 3 (STAT3) that leads to an impaired T_H17 response. STAT3 signaling is also involved in the function of RORγt⁺ type 3 innate lymphoid cells (ILC3s) and RORγt⁺T_H17 cells. The aim of this study was to investigate the role of innate immune cells such as innate lymphoid cells (ILCs), granulocytes, and monocytes in a patient with HIES. Peripheral blood mononuclear cells (PBMCs) from a patient with HIES and three age-matched healthy controls were obtained for the analysis of the innate and adaptive immune cells. The frequencies of ILCs in PBMCs were lower in the patient with HIES than in the controls. Moreover, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-17A produced by ILC3s in PBMCs were lower in the patient with HIES than the controls. Compared with the controls, classical monocytes (CD14⁺CD16^low), which have a high antimicrobial capability, were also lower in the patient with HIES, while non-classical monocytes (CD14^lowCD16⁺) as well as intermediate monocytes (CD14⁺CD16^intermediate) were higher. Taken together, these results indicate that the impaired immune defense against pathogenic microbes in the patient with HIES might be partially explained by functional defects in ILC3s and inflammatory monocytes.

Keywords: Cytokines; Hyper-IgE syndrome; Innate immunity; Innate lymphoid cells; Monocytes; STAT3 transcription factor.

Publication types

Case Reports