National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
National Cancer Institute, National Institutes of Health, Frederick, MD, USA; Department of Medicine and Aging Sciences, University of Chieti-Pescara, Chieti, Italy.
Cytokine. 2022 Dec;160:156049. doi: 10.1016/j.cyto.2022.156049. Epub 2022 Oct 3.
IL-7 is a member of the family of cytokines with four anti-parallel α helixes that bind Type I cytokine receptors. It is produced by stromal cells and is required for development and homeostatic survival of lymphoid cells.
Interleukin 7 (IL7) human IL7: gene ID: 3574 on ch 8; murine Il7 gene ID: 16,196 on ch 3.
Precursor contains a signal sequence, mature human IL-7 peptide 152aa, predicted 17.4kd peptide, glycosylated resulting in 25kd. Crystal structure: http://www.rcsb.org/structure/3DI2. REGULATION OF IL-7 PRODUCTION: Major producers are stromal cells in thymus, bone marrow and lymphoid organs but also reported in other tissues. Production is primarily constitutive but reported to be affected by IFNγ and other factors. IL-7 RECEPTORS: Two chains IL-7Rα (IL-7R) and γc (IL-2RG). Human IL-7R: gene ID 3575 on ch 5; human IL2RG: gene ID 3561 on ch X; mouse IL-7R: gene ID 16,197 on ch 15; murine Il2rg gene ID 16,186 on ch X. Member of γc family of receptors for cytokines IL-2, -4, -9, -15, and -21. Primarily expressed on lymphocytes but reports of other cell types. Expression in T-cells downregulated by IL-7. Low expression on Tregs, no expression on mature B-cells. Crystal structure: http://www.rcsb.org/structure/3DI2. IL-7 RECEPTOR SIGNAL TRANSDUCTION PATHWAYS: Major signals through JAK1, JAK3 to STAT5 and through non-canonical STAT3, STAT1, PI3K/AKT and MEK/ERK pathways. BIOLOGICAL ACTIVITY OF IL-7: Required for survival of immature thymocytes, naïve T-cells, memory T-cells, pro-B-cells and innate lymphocytes. Pharmacological treatment with IL-7 induces expansion of naïve and memory T-cells and pro-B-cells. ABNORMALITIES OF THE IL-7 PATHWAY IN DISEASE: Deficiencies in the IL-7 pathway in humans and mice result in severe combined immunodeficiency due to lymphopenia. Excessive signaling of the pathway in mice drives autoimmune diseases and in humans is associated with autoimmune syndromes including multiple sclerosis, type 1 diabetes, rheumatoid arthritis, sarcoidosis, atopic dermatitis and asthma. Mutations in the IL-7 receptor pathway drive acute lymphoblastic leukemia.
IL-7 has been evaluated in patients with cancer and shown to expand lymphocytes. It accelerated lymphocyte recovery after hematopoietic stem cell transfer, and increased lymphocyte counts in AIDS patients and sepsis patients. Monoclonal antibodies blocking the IL-7 receptor are being evaluated in autoimmune diseases. Cytotoxic monoclonals are being evaluated in acute lymphoblastic leukemia. Drugs blocking the signal transduction pathway are being tested in autoimmunity and acute lymphoblastic leukemia.
白细胞介素 7（IL-7）是细胞因子家族的一员，具有四个反平行的α螺旋，可结合 I 型细胞因子受体。它由基质细胞产生，是淋巴细胞发育和稳态存活所必需的。
白细胞介素 7（IL7）人 IL7：基因 ID：8 号染色体上的 3574；鼠 Il7 基因 ID：3 号染色体上的 16,196。
前体含有信号序列，成熟的人 IL-7 肽 152aa，预测 17.4kd 肽，糖基化导致 25kd。晶体结构：http://www.rcsb.org/structure/3DI2。
白细胞介素 7 产生的调节：主要产生细胞是胸腺、骨髓和淋巴器官中的基质细胞，但也在其他组织中报道。产生主要是组成型的，但据报道受 IFNγ和其他因素的影响。
白细胞介素 7 受体：两个链 IL-7Rα（IL-7R）和γc（IL-2RG）。人 IL-7R：5 号染色体上的基因 ID 3575；人 IL2RG：X 染色体上的基因 ID 3561；鼠 IL-7R：15 号染色体上的基因 ID 16,197；鼠 Il2rg 基因 ID 16,186 在 X 染色体上。白细胞介素 2、-4、-9、-15 和 -21 的 γc 家族细胞因子受体的成员。主要在淋巴细胞上表达，但也有其他细胞类型的报道。T 细胞中的表达被 IL-7 下调。Tregs 中低表达，成熟 B 细胞中无表达。晶体结构：http://www.rcsb.org/structure/3DI2。
白细胞介素 7 受体信号转导途径：主要通过 JAK1、JAK3 传递到 STAT5，通过非经典 STAT3、STAT1、PI3K/AKT 和 MEK/ERK 途径传递。
白细胞介素 7 的生物学活性：存活所需的幼稚胸腺细胞、幼稚 T 细胞、记忆 T 细胞、前 B 细胞和先天淋巴细胞。用白细胞介素 7 进行药物治疗可诱导幼稚和记忆 T 细胞和前 B 细胞的扩增。该途径的异常在疾病中：人和小鼠的 IL-7 途径缺陷导致严重联合免疫缺陷，因为淋巴细胞减少。该途径的过度信号在小鼠中驱动自身免疫疾病，在人类中与包括多发性硬化症、1 型糖尿病、类风湿关节炎、结节病、特应性皮炎和哮喘在内的自身免疫综合征相关。IL-7 受体途径中的突变驱动急性淋巴细胞白血病。
白细胞介素 7 已在癌症患者中进行了评估，结果表明它可扩增淋巴细胞。它加速了造血干细胞移植后的淋巴细胞恢复，并增加了艾滋病患者和败血症患者的淋巴细胞计数。阻断 IL-7 受体的单克隆抗体正在自身免疫性疾病中进行评估。针对急性淋巴细胞白血病的细胞毒性单克隆抗体正在进行评估。阻断信号转导途径的药物正在自身免疫和急性淋巴细胞白血病中进行测试。
