IL-6-targeted therapies to block the cytokine or its receptor drive distinct alterations in T cell function.
IL-6-targeted therapies to block the cytokine or its receptor drive distinct alterations in T cell function.
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DOI：
10.1172/jci.insight.159436
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发表时间：
2022-11-22
期刊：
影响因子：
8
通讯作者：
Buckner, Jane H.
中科院分区：
文献类型：
--
作者：
Speake, Cate;Habib, Tania;Lambert, Katharina;Hundhausen, Christian;Lord, Sandra;Dufort, Matthew J.;Skinner, Samuel O.;Hu, Alex;Kinsman, MacKenzie;Jones, Britta E.;Maerz, Megan D.;Tatum, Megan;Hocking, Anne M.;Nepom, Gerald T.;Greenbaum, Carla J.;Buckner, Jane H.
在其信号通路的不同点抑制IL-6的治疗方法已在临床应用，但这些干预措施的免疫效果是否因其分子靶点而不同尚不清楚。我们使用抗il -6（西妥昔单抗）或抗il -6受体（IL-6R；托珠单抗）对1型糖尿病患者进行了短期干预，并研究了这种体内阻断对T细胞命运和功能的影响。免疫结果受治疗干预目标（IL-6与IL-6R）和峰值药物浓度的影响。Tocilizumab降低了T滤泡辅助细胞群和T细胞受体驱动（tcr驱动）STAT3磷酸化的ICOS表达。西妥昔单抗逆转了treg介导抑制的耐药性，增加了tcr驱动的磷酸化STAT3以及T效应物产生的IL-10、IL-21和IL-27。总之，这些发现表明，体内IL-6阻断的背景可驱动可能影响治疗结果的不同T细胞内在变化。
Therapeutics that inhibit IL-6 at different points in its signaling pathway are in clinical use, yet whether the immunological effects of these interventions differ based on their molecular target is unknown. We performed short-term interventions in individuals with type 1 diabetes using anti–IL-6 (siltuximab) or anti–IL-6 receptor (IL-6R; tocilizumab) therapies and investigated the impact of this in vivo blockade on T cell fate and function. Immune outcomes were influenced by the target of the therapeutic intervention (IL-6 versus IL-6R) and by peak drug concentration. Tocilizumab reduced ICOS expression on T follicular helper cell populations and T cell receptor–driven (TCR-driven) STAT3 phosphorylation. Siltuximab reversed resistance to Treg-mediated suppression and increased TCR-driven phosphorylated STAT3 and production of IL-10, IL-21, and IL-27 by T effectors. Together, these findings indicate that the context of IL-6 blockade in vivo drives distinct T cell–intrinsic changes that may influence therapeutic outcomes.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
DOI：
10.4049/jimmunol.0803721
发表时间：
2009-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Goodman WA;Levine AD;Massari JV;Sugiyama H;McCormick TS;Cooper KD
通讯作者：
Cooper KD
影响因子：
8.2
作者：
Ekman, Ilse;Ihantola, Emmi-Leena;Kinnunen, Tuure
通讯作者：
Kinnunen, Tuure
影响因子：
20.3
作者：
Nishimoto, Norihiro;Terao, Kimio;Kakehi, Takahiro
通讯作者：
Kakehi, Takahiro
影响因子：
7.7
作者：
Lindley, S;Dayan, CM;Tree, TIM
通讯作者：
Tree, TIM