Skip to main content
ISTH 2023 Main banner
Back

    Oral Communication

    Pediatrics

    The Spectrum of Pediatric Bleeding and Clotting: From Genes to Long-Term Related Outcomes

    OC 48.1 - FOXO1 and FOXO3 regulate the proliferation and suppressive function of regulatory T cells in pediatric immune thrombocytopenia

    Monday, June 26, 2023
    14:45 – 15:00 ET
    Room: 518
    Session Available As: On-Demand

      Co-Author(s)

    • XX

      Xingjuan Xie

      Doctor
      Beijing Children's Hospital, Capital Medical University
      Beijing, Beijing, China (People's Republic)

    • Juntao Ouyang

      Master degree candidate
      Beijing Children's Hospital, Capital Medical University
      Beijing, Beijing, China (People's Republic)

    • Hao Gu, MD

      Doctor
      Beijing Children's Hospital, Capital Medical University
      Beijing, Beijing, China (People's Republic)

    • JM

      Jinyao Ma

      Doctor
      Beijing Children's Hospital, Capital Medical University
      Beijing, Beijing, China (People's Republic)

    • RW

      Runhui Wu

      Director and Physician in Chief
      Beijing Children’s Hospital, Capital Medical University, Beijing, China
      Beijing, Beijing, China (People's Republic)

      • Presenting Author(s)

    • Zhenping CHEN, MD

      Beijing Children’s Hospital, Capital Medical University
      Beijing, Beijing, China (People's Republic)

    Background: Immune thrombocytopenia (ITP) is an autoimmune disease with many immune dysfunctions including regulatory T cells (Tregs) deficiency. FOXO1 and FOXO3 have been proven crucial for T cell differentiation and activation. However, there is still a lack of research on FOXO1/FOXO3 in the pathogenesis of pediatric ITP.

    Aims: This study aimed to determine the effects of FOXO1/FOXO3 on the differentiation and suppressive function of Tregs in children with ITP.

    Methods: We enrolled 15 children with newly diagnosed ITP(NITP), 15 chronic ITP( CITP), and 10 healthy controls (HCs) in this study. The expression of FOXO1, and FOXO3 were detected by RT-qPCR, Western blotting, and flow cytometry. The Tregs suppression assay was performed to evaluate the function of Tregs isolated from ITP patients. CD4+ T cells isolated from ITP patients and HCs were cultured in vitro with or without FOXO1 inhibitor (AS1842856), in which the proportion and suppression assay of Tregs were measured.

    Results: The proportion and function of Tregs were reduced in CITP patients when compared with HCs and NITP patients (P < 0.05). Both FOXO1 and FOXO3 mRNA expression levels were significantly lower in PBMCs of chronic ITP (CITP) than HCs (P = 0.036, P = 0.048, respectively), but no differences between HCs and NITP. The patients with CITP had lower protein expressions of FOXO1 and FOXO3, and higher ratios of phospho-FOXO1/FOXO1 and phospho-FOXO3/FOXO3 than HCs and NITP. The percentage of Tregs in CD4+ T cells was positively correlated with the expressions of FOXO1 and FOXO3, but negatively correlated with the ratios of phospho-FOXO1/FOXO1 and phospho-FOXO3/FOXO3. In the coculture systems of CD4+ T cells, AS1842856 significantly impaired the differentiation and suppressive function of Tregs.

    Conclusion(s): The downregulation of the FOXO1 and FOXO3 may be a critical cause of Treg dysfunction in pediatric CITP.

    Learning Objectives:

    • Upon completion, participants will able to recognize the dysfunction of Treg in pediatric ITP. Significantly decreased frequency and impaired immunosuppressive function of Treg cells in patients with CITP compared to NITP.
    • Upon completion, participants will able to differentiate the expression of FOXO1 and FOXO3 between CITP and NITP. Lower FOXO1 expression and higher phosphorylated-FOXO1 were found in CITP rather than NITP.
    • Upon completion, participants will able to understand the mechanism by which FOXO1 impairs Tregs function leading to pediatric CITP. Inhibiting the activity of FOXO1 suppressed proliferation and function of Treg cells in vitro.