Defective Toll-Like Receptors Driven B Cell Response in Hyper IgE Syndrome Patients With STAT3 Mutations

Ruolan Gong; Jing Wu; Jing Wu; Yingying Jin; Yingying Jin; Tongxin Chen; Tongxin Chen; Tongxin Chen

doi:10.3389/fped.2021.738799

Frontiers in Pediatrics (Nov 2021)

Defective Toll-Like Receptors Driven B Cell Response in Hyper IgE Syndrome Patients With STAT3 Mutations

Ruolan Gong,
Jing Wu,
Jing Wu,
Yingying Jin,
Yingying Jin,
Tongxin Chen,
Tongxin Chen,
Tongxin Chen

Affiliations

Ruolan Gong: Division of Immunology, Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Jing Wu: Division of Immunology, Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Jing Wu: Allergy/Immunology Innovation Team, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Yingying Jin: Allergy/Immunology Innovation Team, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Yingying Jin: Department of Rheumatology/Immunology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Tongxin Chen: Division of Immunology, Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Tongxin Chen: Allergy/Immunology Innovation Team, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Tongxin Chen: Department of Rheumatology/Immunology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

DOI: https://doi.org/10.3389/fped.2021.738799
Journal volume & issue: Vol. 9

Abstract

Read online

Autosomal dominant hyper-IgE syndrome (AD-HIES) is a rare inherited primary immunodeficient disease (PIDs), which is caused by STAT3 gene mutations. Previous studies indicated a defective Toll-like receptor (TLR) 9-induced B cell response in AD-HIES patients, including proliferation, and IgG production. However, the other TLRs-mediated B cell responses in AD-HIES patients were not fully elucidated. In this study, we systematically studied the B cell response to TLRs signaling pathways in AD-HIES patients, including proliferation, activation, apoptosis, cytokine, and immunoglobulin production. Our results showed that the TLRs-induced B cell proliferation and activation was significantly impaired in AD-HIES patients. Besides, AD-HIES patients had defects in TLRs-induced B cell class switch, as well as IgG/IgM secretion and IL-10 production in B cells. Taken together, we first systematically reported the deficiency of TLRs driven B cell response in AD-HIES patients, which help to have a better understanding of the pathology of AD-HIES.

Published in Frontiers in Pediatrics

ISSN: 2296-2360 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Pediatrics
Website: http://journal.frontiersin.org/journal/pediatrics

About the journal

Abstract

Keywords