The Potential of Harnessing IL-2-Mediated Immunosuppression to Prevent Pathogenic B Cell Responses.
The Potential of Harnessing IL-2-Mediated Immunosuppression to Prevent Pathogenic B Cell Responses.
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DOI：
10.3389/fimmu.2021.667342
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发表时间：
2021
影响因子：
7.3
通讯作者：
Ballesteros-Tato A
中科院分区：
文献类型：
--
作者：
Papillion A;Ballesteros-Tato A
免疫抑制药物可以部分控制抗体 (Ab) 依赖性病理。然而，这些治疗方案必须在患者的一生中维持，这通常会带来严重的副作用。随着研究的进展，我们对自身反应性 B 细胞反应的发展和维持的细胞和分子机制的理解有了显着的进步。因此，旨在恢复自身免疫患者免疫耐受并预防疾病进展的新型免疫疗法正在进行中。在这方面，临床和临床前研究的令人鼓舞的结果表明，皮下注射低剂量的重组白介素-2 (r-IL2) 对患有自身免疫性疾病的患者具有有效的免疫抑制作用。尽管 IL-2 诱导免疫抑制的确切机制尚不清楚，但当前基于 IL-2 的免疫疗法的临床益处归因于其对增强 T 调节 (Treg) 细胞的作用，已知 Treg 细胞可以抑制过度活跃的免疫反应。然而，除了 Tregs 之外，rIL-2 还直接阻止滤泡辅助 T 细胞 (Tfh)、辅助 T 细胞 17 细胞 (Th17) 和双阴性 (DN) T 细胞反应，这些细胞在自身免疫性疾病的发展中发挥着关键作用，并有能力帮助致病性 B 细胞。在这里，我们讨论了 rIL-2 免疫疗法的更广泛影响，以及将 rIL-2 与其他基于细胞因子的疗法相结合以更有效地靶向 Tfh 细胞、Th17 和 DN T 细胞并随后抑制自身免疫患者中自身抗体 (ab) 产生的潜力。
Immunosuppressive drugs can partially control Antibody (Ab)-dependent pathology. However, these therapeutic regimens must be maintained for the patient’s lifetime, which is often associated with severe side effects. As research advances, our understanding of the cellular and molecular mechanisms underlying the development and maintenance of auto-reactive B cell responses has significantly advanced. As a result, novel immunotherapies aimed to restore immune tolerance and prevent disease progression in autoimmune patients are underway. In this regard, encouraging results from clinical and preclinical studies demonstrate that subcutaneous administration of low-doses of recombinant Interleukin-2 (r-IL2) has potent immunosuppressive effects in patients with autoimmune pathologies. Although the exact mechanism by which IL-2 induces immunosuppression remains unclear, the clinical benefits of the current IL-2-based immunotherapies are attributed to its effect on bolstering T regulatory (Treg) cells, which are known to suppress overactive immune responses. In addition to Tregs, however, rIL-2 also directly prevent the T follicular helper cells (Tfh), T helper 17 cells (Th17), and Double Negative (DN) T cell responses, which play critical roles in the development of autoimmune disorders and have the ability to help pathogenic B cells. Here we discuss the broader effects of rIL-2 immunotherapy and the potential of combining rIL-2 with other cytokine-based therapies to more efficiently target Tfh cells, Th17, and DN T cells and subsequently inhibit auto-antibody (ab) production in autoimmune patients.
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影响因子：
32.4
作者：
Choi YS;Kageyama R;Eto D;Escobar TC;Johnston RJ;Monticelli L;Lao C;Crotty S
通讯作者：
Crotty S
影响因子：
3.2
作者：
Brand, Oliver J.;Lowe, Christopher E.;Gough, Stephen C. L.
通讯作者：
Gough, Stephen C. L.
影响因子：
2.8
作者：
Ballesteros-Tato A
通讯作者：
Ballesteros-Tato A
DOI：
10.1073/pnas.0807309106
发表时间：
2009-02-03
影响因子：
11.1
作者：
Bubier, Jason A.;Sproule, Thomas J.;Roopenian, Derry C.
通讯作者：
Roopenian, Derry C.
影响因子：
15.3
作者：
Ansel, K M;McHeyzer-Williams, L J;Ngo, V N;McHeyzer-Williams, M G;Cyster, J G
通讯作者：
Cyster, J G