Upregulated complement receptors correlate with Fc gamma receptor 3A-positive natural killer and natural killer-T cells in neuromyelitis optica spectrum disorder.
Upregulated complement receptors correlate with Fc gamma receptor 3A-positive natural killer and natural killer-T cells in neuromyelitis optica spectrum disorder.
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DOI：
10.1186/s12974-022-02661-1
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发表时间：
2022-12-12
影响因子：
9.3
通讯作者：
中科院分区：
文献类型：
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使用依库珠单抗抑制视神经脊髓炎谱系疾病 (NMOSD) 的终末补体有助于预防复发，但该药物的确切作用机制仍不清楚。同样，Fc Gamma 受体 3A (FCGR3A)（也称为 CD16）的遗传变异与 NMOSD 的结果相关，但表达这些 CD16 的免疫细胞尚不清楚。我们将 NMOSD 中自然杀伤 (NK) 细胞和自然杀伤 T (NKT) 细胞中受补体活性调节的免疫细胞上的 CD16 表达与疾病和正常健康对照进行了比较。对 45 名携带水通道蛋白 4 (AQP4)-IgG 的 NMOSD 患者、18 名疾病对照者和 19 名正常对照者的外周血细胞 (PBMC) 样本进行体外 CD16 表达和补体受体分析。基线时，NMOSD 中 NKT 细胞数量增加 (p<0.001)，但与正常对照和疾病对照相比，CD16 阳性比例较低 (p=0.0012)。 NK 细胞计数正常，但 CD16 阳性的比例也显着降低 (p<<0.001)。在来自 NMOSD 的 NK 细胞和 NKT 细胞中，C5 补体受体表达远高于正常和疾病对照（两者均 p<0.001）。我们还评估了激活标记物 CD69 和 CD83，它们在 NMOSD 患者的 NK 和 NKT 细胞中也显着较高。 NMOSD 患者中 FCGR3A p158 V/V 基因型组表现出随着激活而减少的 NK 细胞比例，并且表达 CD16 的 NKT 细胞比 F/F 基因型组更少。我们的结果支持免疫发病机制模型，其中 NK/NKT 细胞中的补体途径激活上调与抗体/抗原复合物结合的 CD16 表达。在 NMOSD 的背景下，这些补体敏感细胞可能是自身免疫活动不断升级的原因。在线版本包含可在 10.1186/s12974-022-02661-1 获取的补充材料。
Inhibition of terminal complement in neuromyelitis optica spectrum disorder (NMOSD) using eculizumab helps prevent relapses, but the exact mechanism of action of the drug remains unclear. Similarly, genetic variants in the Fc Gamma receptor 3A (FCGR3A), also known as CD16, are correlated with outcomes in NMOSD, but the immune cells expressing those CD16 are unknown. We compared CD16 expression on immune cells modulated by complement activity in natural killer (NK) cells and natural killer-T (NKT) cells in NMOSD to disease and normal-healthy controls. Peripheral blood cell (PBMC) samples from 45 patients with NMOSD with aquaporin 4 (AQP4)-IgG, 18 disease controls, and 19 normal controls were analyzed for CD16 expression and complement receptors in vitro. At baseline, the number of NKT cells was increased in NMOSD (p < 0.001), but the proportion that was CD16 positive was lower compared to normal and disease controls (p = 0.0012). NK cell count was normal, but the ratio that was CD16 positive was also significantly lower (p < 0.001). In both NK cells and NKT cells from NMOSD, C5 complement receptor expression was much higher than normal and disease controls (p < 0.001 for both). We also evaluated activation markers CD69 and CD83, which were also significantly higher in NK and NKT cells from NMOSD patients. FCGR3A p158 V/V genotype group in NMOSD patients showed decreased NK cell proportion with activation, and fewer CD16-expressing NKT cells than the F/F genotype group. Our results support an immunopathogenesis model in which complement pathway activation in NK/NKT cells upregulates CD16 expression that binds to antibody/antigen complexes. In the context of NMOSD, these complement-sensitive cells may be responsible for the escalating autoimmune activity. The online version contains supplementary material available at 10.1186/s12974-022-02661-1.
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影响因子：
3.7
作者：
Chihara N;Aranami T;Oki S;Matsuoka T;Nakamura M;Kishida H;Yokoyama K;Kuroiwa Y;Hattori N;Okamoto T;Murata M;Toda T;Miyake S;Yamamura T
通讯作者：
Yamamura T
影响因子：
9.3
作者：
通讯作者：
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外周血CD5（+）CD19（+）B细胞的频率，CD3（ - ）CD16（+）CD56（+）NK和CD3（+）CD56（+）CD56（+）NKT细胞和血清白介素10的患者硬化症和神经瘤谱谱障碍。
DOI：
10.1186/s13223-021-00596-5
发表时间：
2022-01-14
期刊：
Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology
影响因子：
--
作者：
Khani L;Jazayeri MH;Nedaeinia R;Bozorgmehr M;Nabavi SM;Ferns GA
通讯作者：
Ferns GA
影响因子：
4
作者：
Flanagan, Eoin P.;Levy, Michael;Cree, Bruce A. C.
通讯作者：
Cree, Bruce A. C.
DOI：
10.4049/jimmunol.1100338
发表时间：
2011-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Fusakio ME;Mohammed JP;Laumonnier Y;Hoebe K;Köhl J;Mattner J
通讯作者：
Mattner J