选择性激动KIR和NKG2A,以逃避自然杀手细胞缺失的自我反应
Satoshi Hiura1, Yuto Kuwasaki2, Yosuke Nishikawa3
1Discovery Research Laboratories V, Daiichi Sankyo Co., Ltd., Tokyo, Japan. satoshi.hiura@daiichisankyo.com.
Scientific reports
|September 29, 2025
概括
研究人员开发了新型激动剂,以抑制自然杀手 (NK) 细胞对异构诱导多能干细胞 (allo-iPSC) 疗法的排斥. 这一突破提高了免疫耐受性,为使用合金-iPSCs的先进再生医学铺平了道路.
科学领域:
- 免疫学 免疫学 免疫学
- 干细胞生物学 干细胞生物学
- 再生医学是一种再生医学.
背景情况:
- 同源移植面临免疫排斥的挑战,特别是诱导多能干细胞 (iPSC) 衍生疗法.
- 人类白细胞抗原 (HLA) 类 I 缺陷的 iPSCs 逃避 T 细胞排斥,但通过缺失自我反应被自然杀手 (NK) 细胞准.
- 现有的使用化学HLA-E抑制NKG2A表达NK细胞的策略对于NKG2A阴性NK细胞是不够的.
研究的目的:
- 开发新的策略来克服NK细胞介导的HLA类I缺陷iPSCs的排斥.
- 为了确定向NK细胞上抑制杀手免疫球蛋白受体 (KIRs) 的激动剂.
- 增强对所有基因诱导多能干细胞 (allo-iPSC) 疗法的免疫耐受性.
主要方法:
- 开发用于抑制KIR的选择性激动剂 (KIR2DL1,KIR2DL2/3,KIR3DL1).
- 测试这些KIR激动剂在抑制NK细胞对HLA类I缺陷iPSCs的活性方面的有效性.
- 鉴定一种NKG2A选择性激动剂,同时也刺激NKG2C激活受体.
主要成果:
- 选择性抑制KIR激动剂已开发并证明可以抑制NK细胞介导的排斥.
- 在T细胞和HLA类I缺陷iPSC上引入这些激动剂促进了免疫逃避.
- 鉴定出一种NKG2A选择性激动剂,可以作为化学HLA-E的潜在替代品,增强免疫耐受性.
结论:
- 新型KIR激动剂和NKG2A选择性激动剂为缓解合金iPSC疗法中NK细胞排斥提供了有希望的策略.
- 这项技术显著提高了对iPSC衍生细胞疗法的免疫耐受性.
- 这些发现有助于推进基于iPSC的再生医学.
相关概念视频
Cells of the Innate Immune Response
8.7K
The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
8.7K
Cytotoxic T Cells-mediated Immune Response
6.5K
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
6.5K
Immune Surveillance by NK Cells and Phagocytes
7.9K
Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
7.9K
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
588
Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy. SP binds and activates...
588
Antigens Involved in Adaptive Immunity
1.3K
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and...
Complete Antigens
Complete antigens possess both immunogenicity and...
1.3K
Immune Response Against Viral Pathogens
1.8K
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
1.8K


