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The Importance of C5aR2 in Neutrophil Function and Its Impact on Neutrophil-mediated Diseases C5aR2在中性粒细胞功能中的重要性及其对中性粒细胞介导疾病的影响
Pub Date : 2022-12-31 DOI: 10.33696/immunology.4.150
Daniel Leonard Seiler, Marie Kleingarn, Syeda Zoela Gilani, Paula Emily Reichel, Jörg Köhl, C. Karsten
The two receptors for the anaphylatoxin C5a are critically involved in the recruitment of immune cells and activate these cells at sites of inflammation. The pro-inflammatory function of C5aR1 in these processes is well established, whereas the functional properties of the second C5a receptor, C5aR2, in inflammation remain enigmatic. We recently reported a pro-inflammatory contribution of C5aR2 to the pathogenesis of the prototypical autoimmune skin blistering disease epidermolysis bullosa acquisita (EBA). Deficiency of C5aR2 ameliorated the disease phenotype in an antibody transfer model of EBA and reduced neutrophil migration and activation in vitro . Here, we discuss not only these data, but the crosstalk of C5aR2 with Fcγ receptors, and the effect of C5a desArg stimulation on neutrophils. In addition, we highlight the cellular location of C5aR2, its functional dependence on concomitant C5aR1 expression, and its importance for therapeutic strategies targeting the C5a receptor pathways in neutrophil-mediated diseases.
过敏毒素C5a的两种受体在免疫细胞的募集和炎症部位激活这些细胞中起关键作用。C5aR1在这些过程中的促炎功能已经确定,而第二种C5a受体C5aR2在炎症中的功能特性仍然是谜。我们最近报道了C5aR2在典型自身免疫性皮肤水疱病大疱性表皮松解症(EBA)发病机制中的促炎作用。在EBA抗体转移模型中,缺乏C5aR2改善了疾病表型,并减少了中性粒细胞在体外的迁移和活化。在这里,我们不仅讨论了这些数据,还讨论了C5aR2与Fcγ受体的串扰,以及C5a设计arg刺激对中性粒细胞的影响。此外,我们强调了C5aR2的细胞定位,其功能依赖于伴随的C5aR1表达,以及在中性粒细胞介导的疾病中针对C5a受体途径的治疗策略的重要性。
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引用次数: 2
Is Omicron Variant of COVID-19 Threatening Health Like Other Variants? COVID-19的Omicron变体像其他变体一样威胁健康吗?
Pub Date : 2022-12-31 DOI: 10.33696/immunology.4.154
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引用次数: 0
Vγ2+ γδ T Cells and Their Regulatory Potential in Skin Allograft Survival Vγ2+γδT细胞及其在同种异体皮肤移植中的调节作用
Pub Date : 2022-12-31 DOI: 10.33696/immunology.4.153
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引用次数: 0
Going above and Beyond: Using an Attenuated Herpes Viral Vaccine Vector to Elicit Protective Immune Responses Through Neutralizing and Non-neutralizing Functions of Antibodies 超越:使用减毒疱疹病毒疫苗载体通过抗体的中和和非中和功能引发保护性免疫反应
Pub Date : 2022-12-09 DOI: 10.33696/immunology.4.149
Katherine E. Kaugars, Angelo R. Retamal-Diaz, Anna Paula de Oliveira, P. González, W. Jacobs
Protective
保护
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引用次数: 0
Profiling Proteasome Activities in Peripheral Blood – A Novel Biomarker Approach 分析外周血中蛋白酶体的活性-一种新的生物标志物方法
Pub Date : 2022-12-09 DOI: 10.33696/immunology.4.147
L. Bramasole, S. Meiners
A
英语字母表的第1个字母
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引用次数: 1
Sialyllactose Prevents Cartilage Damages via M0 Macrophage Maintenance in Yucatan Mini-Pig Osteoarthritis Model 唾液乳糖通过M0巨噬细胞维持预防尤卡坦小型猪骨关节炎模型软骨损伤
Pub Date : 2022-12-09 DOI: 10.33696/immunology.4.145
Kyung-Tai Kim, Young-Kyu Kim, Mi-Jin Yang, Min-young Kim, Lila Kim, J. Hwang
. Sialyllactose Prevents Cartilage Damages via M0 Macrophage Maintenance in Yucatan Mini-Pig Osteoarthritis Model. J Cell Immunol. 2022;4(5):158-166.
在尤卡坦小型猪骨关节炎模型中,唾液乳糖通过M0巨噬细胞维持预防软骨损伤。细胞免疫学杂志。2022年;4(5):158-166。
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引用次数: 0
CAR Therapy for T-cell Malignancies CAR治疗T细胞恶性肿瘤
Pub Date : 2022-09-29 DOI: 10.33696/immunology.4.141
Andrew Cinquina, Jia Feng, Hongyu Zhang, Yupo Ma
The introduction of chimeric antigen receptor (CAR) immunotherapy has been revolutionary in the treatment of hematological malignancies [1]. Remarkable success has been achieved in the clinical treatment of B-cell malignancies through the use of CD19 CARs [2-7]. However, translation of CAR therapy for T-cell malignancies has been more difficult for several reasons. As the CAR cells predominantly used are T cells, a CAR T cell manufactured to target malignant T cells using T-cell markers is at risk for fratricide. This would prevent the expansion of the CAR T cell population necessary for proper tumor eradication. Additionally, as both malignant and non-malignant express these T-cell markers, there is concern that a T-cell-directed CAR cell would lead to T-cell deficiency and subsequent opportunistic infections.
嵌合抗原受体(CAR)免疫疗法的引入在治疗血液系统恶性肿瘤方面具有革命性[1]。CD19 CARs在B细胞恶性肿瘤的临床治疗中取得了显著成功[2-7]。然而,由于几个原因,CAR治疗T细胞恶性肿瘤的转化变得更加困难。由于主要使用的CAR细胞是T细胞,因此使用T细胞标记物靶向恶性T细胞而制造的CAR T细胞有自相残杀的风险。这将阻止正确根除肿瘤所必需的CAR T细胞群的扩增。此外,由于恶性和非恶性都表达这些T细胞标志物,人们担心T细胞导向的CAR细胞会导致T细胞缺乏和随后的机会性感染。
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引用次数: 0
Manufacturing of Human T-lymphoid Progenitors from Two Different Hematopoietic Stem Cell Sources and Perspective for New Immunotherapies 两种不同造血干细胞来源制造人t淋巴细胞祖细胞及新免疫疗法的前景
Pub Date : 2022-09-28 DOI: 10.33696/immunology.4.144
P. Gaudeaux, R. D. Moirangthem, Pauline Rault, H. Sadek, F. Carbone, Marieke, Lavaert, A. Joshi, T. Taghon, I. André, O. Nègre, T. Soheili
Manufacturing of Human T-lymphoid Progenitors from Two Different Hematopoietic Stem Cell Sources and Perspective for New Immunotherapies. Abstract The adaptive immune system depends on the efficient response of lymphocytes, protecting the organism from infection or malignant diseases. T-cell immunodeficiency, innate or acquired, put the patient at risk for developing opportunistic infections and cancers. We previously described a novel approach to overcome the major limitations of T-cell immunotherapy and hematopoietic stem cell transplant (HSCT) by transplanting human T-lymphoid progenitors (HTLP), with the aim to achieve shortened immune reconstitution and fully functional naïve T-cell repertoire in immunodeficient or immunocompromised patients. By complementing our DL4-based cell culture with TNFα we developed and scaled-up clinical strategies involving hematopoietic stem and progenitor cells (HSPC) differentiated into T-lymphoid progenitors. We discuss here recent advances made in the characterization of different cell sources used as starting materials for T-lymphoid progenitors manufacturing, as well as gene modification of these cells, highlighting new perspectives for the development of therapeutical strategies.
从两种不同的造血干细胞来源制备人T淋巴细胞祖细胞和新免疫疗法的前景。摘要适应性免疫系统依赖于淋巴细胞的有效反应,保护机体免受感染或恶性疾病。先天性或后天性T细胞免疫缺陷使患者面临机会感染和癌症的风险。我们之前描述了一种新的方法,通过移植人类T淋巴细胞祖细胞(HTLP)来克服T细胞免疫疗法和造血干细胞移植(HSCT)的主要局限性,目的是在免疫缺陷或免疫功能低下的患者中实现缩短的免疫重建和全功能的幼稚T细胞库。通过用TNFα补充我们基于DL4的细胞培养,我们开发并扩大了涉及造血干细胞和祖细胞(HSPC)分化为T淋巴细胞祖细胞的临床策略。我们在这里讨论了用作T淋巴细胞祖细胞制造起始材料的不同细胞源的表征以及这些细胞的基因修饰方面的最新进展,强调了治疗策略发展的新前景。
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引用次数: 1
Improvement of the Specificity of the Indirect BAT for the Diagnosis of Peanut Allergy; the BA(Blocking Antibodies)-BAT 间接BAT对花生过敏诊断特异性的提高BA(阻断抗体)-BAT
Pub Date : 2022-09-28 DOI: 10.33696/immunology.4.143
Janneke Ruinemans-Koerts, Monique van Uum-Otters, Don van Baar, J. V. Neerven, Judit Wesseling
These false-positive outcomes can be a consequence of IgE binding to an epitope in the food protein used in these tests that may be inactivated after consumption due to food processing or digestion. Alternatively, the BAT protocol can be less sensitive to interference of inhibiting factors such as allergen specific IgG4 and IgA produced during tolerance development due to e.g. consumption of trace amounts of allergen. However, the influence of inhibiting factors can be detected when allergens are pre-incubated with serum, allowing IgG/IgA binding to allergens, before addition to basophils, as shown by the fact that a decrease in basophil sensitivity to Ara h2 predicted sustained unresponsiveness after peanut oral immunotherapy [4]. In our recent study on the indirect BAT for the diagnosis of peanut allergy we observed a few false-positive BAT outcomes [3]. We hypothesized that these false-positive BAT outcomes might among others be due to inhibiting factors, like IgG4 and IgA, produced during natural tolerance development which effect on basophil activation can’t be adequately detected in the regular BAT protocol. Therefore, we re-analysed with a modified indirect BAT protocol (called “BA(blocking antibodies)-BAT”) the serum samples (n=3) from our indirect BAT peanut study with a false-positive BAT Ara h2 or Ara h6 outcome.
这些假阳性结果可能是这些测试中使用的食物蛋白中的IgE与表位结合的结果,该表位可能在食用后由于食物加工或消化而失活。另外,由于摄入了微量的过敏原,BAT方案可能对诸如在耐受性发展过程中产生的过敏原特异性IgG4和IgA等抑制因子的干扰不太敏感。然而,当将过敏原与血清预先孵育,允许IgG/IgA与过敏原结合,然后再加入嗜碱性粒细胞时,可以检测到抑制因子的影响,如嗜碱性粒细胞对Ara h2敏感性的降低预测花生口服免疫治疗[4]后持续无反应性。在我们最近对间接BAT诊断花生过敏的研究中,我们观察到一些BAT假阳性结果bbb。我们假设这些假阳性BAT结果可能是由于在自然耐受性发育过程中产生的抑制因子,如IgG4和IgA,这些抑制因子对嗜碱性粒细胞激活的影响在常规BAT协议中无法充分检测到。因此,我们使用改进的间接BAT方案(称为“BA(阻断抗体)-BAT”)重新分析了间接BAT花生研究中含有假阳性BAT Ara h2或Ara h6结果的血清样本(n=3)。
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引用次数: 0
Persistence, Pathogenicity and Plasticity: The Role of IL-23 in Th17 Fate 持久性、致病性和可塑性:IL-23在Th17细胞命运中的作用
Pub Date : 2022-09-28 DOI: 10.33696/immunology.4.140
Jens C. Kleiner, Christian F. Krebs
For a long time Th1 cells were considered the key players in the induction of inflammation and progression of disease in autoimmune diseases. With the discovery of IL-17-producing CD4 + T cells (Th17) being abundant at inflammation sites, this soon changed. Investigating this new T helper subset, it became clear that in comparison to Th1 and Th2 cells, Th17 cells have an increased tendency to change their phenotype and therefore become either more pathogenic or immunoregulatory. This makes them an attractive target for therapeutic interventions. As plasticity of Th17 cells differs between different autoimmune diseases, understanding its drivers is complex. This review focusses on the role of plasticity within Th17 cells in induction, aggravation and resolution of disease and points out IL-23 as a potential key player in controlling Th17 fate. Finally, current treatments targeting IL-23 and Th17 plasticity are highlighted and an outlook on future therapeutics is given.
长期以来,Th1细胞被认为是自身免疫性疾病中炎症诱导和疾病进展的关键角色。随着在炎症部位发现大量产生il -17的CD4 + T细胞(Th17),这种情况很快发生了变化。研究这个新的辅助性T细胞亚群,很明显,与Th1和Th2细胞相比,Th17细胞更倾向于改变其表型,因此变得更具致病性或免疫调节性。这使它们成为治疗干预的一个有吸引力的目标。由于不同自身免疫性疾病中Th17细胞的可塑性不同,了解其驱动因素是复杂的。本文综述了Th17细胞可塑性在疾病的诱导、加重和消退中的作用,并指出IL-23可能是控制Th17命运的关键因素。最后,重点介绍了目前针对IL-23和Th17可塑性的治疗方法,并对未来治疗方法进行了展望。
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Journal of cellular immunology
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