2. Academic Validation
  3. PGRN Inhibits Early B-cell Activation and IgE Production Through the IFITM3-STAT1 Signaling Pathway in Asthma

PGRN Inhibits Early B-cell Activation and IgE Production Through the IFITM3-STAT1 Signaling Pathway in Asthma

  • Adv Sci (Weinh). 2024 Oct 16:e2403939. doi: 10.1002/advs.202403939.
Pingping Zhang 1 2 3,  Changshun Ruan 4,  Guangli Yang 1 2 3,  Yaning Guan 1 2 3,  Yin Zhu 1 2 3,  Qian Li 1 2 3,  Xin Dai 5 6,  Yang An 1 2 3,  Xiaoqi Shi 1 2 3,  Pei Huang 1 2 3,  Yan Chen 1 2 3,  Zhixu He 1 2 3,  Zuochen Du 1 2 3,  Chaohong Liu 7
Affiliations

Affiliations

  • 1 Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, China.
  • 2 Department of Pediatrics, Guizhou Children's Hospital, Zunyi, 563000, China.
  • 3 Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine of Zunyi Medical University, Zunyi, 563099, China.
  • 4 Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
  • 5 Zhanjiang Institute of Clinical Medicine, Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang, 524037, China.
  • 6 Department of Hematology, Central People's Hospital of Zhanjiang, Zhanjiang, 524037, China.
  • 7 Department of Pathogen Biology School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology Wuhan Hubei China, Hubei, 430074, China.
PMID: 39412083 DOI: 10.1002/advs.202403939
Abstract

Progranulin (PGRN) plays a critical role in bronchial asthma and the function of various immune cells. However, the mechanisms by which PGRN influences B-cell receptor (BCR) signaling and immunoglobulin E(IgE) production are not fully understood. The study aimed to elucidate the molecular mechanisms through which PGRN affects BCR signaling, B-cell differentiation, and IgE production. A PGRN knockout mouse model, along with techniques including flow cytometry, the creation of a bone marrow chimeric mouse model, total internal reflection fluorescence (TIRF), and Western blot (WB) analysis is employed, to investigate the link between PGRN and various aspects of B-cell biology. It is discovered that the absence of PGRN in mice alters peripheral B-cell subpopulations, promotes IgE class switching in a cell-intrinsic manner, and affects B-cell subpopulations. Additionally, PGRN modulates B-cell functions by regulating BCR signaling pathways, metabolic processes, and the actin Cytoskeleton during early B-cell activation. Significantly, PGRN deficiency results in diminished production of NP-specific Antibodies. Moreover, it is found that PGRN inhibits B-cell activation and IgE production through the PGRN-IFITM3-STAT1 signaling pathway. The findings provide new strategies for the targeted treatment of bronchial asthma, highlighting the crucial role of PGRN in B-cell signaling and IgE production.

Keywords

BCR signaling; IFITM3; IgE; asthma; progranulin.

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