Mechanisms of Fetal and Neonatal Immunosuppression by Nucleated Erythrocytes

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16914
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: University of Tsukuba
• Principal Investigator: Takeuchi Shusuke 筑波大学, 附属病院, 病院助教 (80828046)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ハプトグロビン / 有核赤血球 / 臍帯血 / IL-10 / 自然免疫

Outline of Final Research Achievements

We have hypothesize previously shown that cord blood-derived CD45-NRBCs and adult peripheral blood-derived monocytes under LPS stimulated indirect co-culture system, increased IL-10 and decreased TNF-α secretion which suggests the immunosuppressive function of CD45-NRBCs via unknown soluble factor. We hypothesized that NRBCs secrete haptoglobin and induce immunosuppressive function of monocytes by activating the CD163-HO-1 axis. We confirmed the immunosuppressive function of CD45-NRBC by co-culturing with cord blood derived monocytes under LPS stimulation in indirect co-culture system. Immunosuppressive response decreased when the co-culture medium was supplemented with anti-CD163 blocking antibody or HO-1 inhibitor ZnPP-IX. Haptoglobin levels in the culture medium with NRBCs were high and expressed haptoglobin gene. Thus, CD45-NRBCs secrete haptoglobin and activates the immunosuppressive function of monocytes.

Free Research Field

小児科学

Academic Significance and Societal Importance of the Research Achievements

有核赤血球はハプトグロビンの産生を介して胎児期の免疫抑制環境の維持に関与している可能性がある。また、有核赤血球は胎児期のみならず敗血症や自己炎症性疾患などでも末梢血中に出現する。成人骨髄由来有核赤血球もハプトグロビン遺伝子の増加が示されており、周産期だけでなく小児期以降にも免疫抑制機構として作用している可能性がある。