Potential for TCDD to induce regulatory functions in B cells as part of the mechanism for T cell suppression in EAE.

Potential for TCDD to induce regulatory functions in B cells as part of the mechanism for T cell suppression in EAE.
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DOI:
10.1016/j.taap.2022.116259
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发表时间:
2022-11-01
影响因子:
3.8
通讯作者:
Kaplan, Barbara L. F.
Kaplan, Barbara L. F.
中科院分区:
医学3区
文献类型:
--
作者:
McDonald, Amye;Nicaise, Ashleigh;Sears, Erin Rushing;Bell, Abigail;Kummari, Evangel;Kaplan, Barbara L. F.

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2,3,7.8-四氯二苯并-对二恶英 (TCDD) 抑制免疫功能的部分机制涉及诱导调节性 T 细胞和抑制效应 T 细胞。该项目的目标是检查 TCDD 对效应 T 细胞的抑制是否部分归因于诱导 B 调节细胞 (Bregs)。 TCDD 增加 CD24+CD38+ B 细胞百分比和/或功能的潜力通过体外脂多糖 (LPS) + 白细胞介素 (IL)-4 和体内实验性自身免疫性脑脊髓炎 (EAE) 轻度模型的反应进行了评估。在体外,TCDD 并没有一致地增加使用脾细胞、纯化的 B 细胞或骨髓 (BM) 细胞的 CD19+CD24+CD38+ 细胞的百分比。然而,TCDD 增加了所有三种培养物制剂中的 IL-10,并且 TCDD 增加了产生 IL-10 的 CD5+CD24+CD38+ 细胞的百分比。在 EAE 中,TCDD 不影响终末期疾病时脾细胞 (SPLC)、淋巴结 (LN) 或 BM 细胞中 CD19、B220 或 CD5 B 细胞中 CD24+CD38+ 细胞群的百分比。另一方面,TCDD 增加了 EAE 中脊髓 (SC) 中 CD19+CD24+CD38+ 的百分比。此外,从脾脏中分离的 TCDD 处理的 B 细胞或 EAE 小鼠中经 TCDD 处理的 BM 细胞适度降低了幼稚效应 T 细胞表达干扰素 (IFN)-γ 和肿瘤坏死因子 (TNF)-α 的能力。这些数据共同表明 TCDD 可以诱导 B 细胞的调节功能,尽管仅通过检查调节标记的表达但通过细胞因子产生或混合淋巴细胞反应评估功能并不明显。
Part of the mechanism by which 2,3,7.8-tetrachlorodibenzo-p-dioxin (TCDD) suppresses immune function involves induction of regulatory T cells and suppression of effector T cells. The goal of this project was to examine whether TCDD’s suppression of effector T cells was due in part to inducing B regulatory cells (Bregs). TCDD’s potential to increase the percentage and/or function of CD24+CD38+ B cells was assessed in response to lipopolysaccharide (LPS) + interleukin (IL)-4 in vitro and in a mild model of experimental autoimmune encephalomyelitis (EAE) in vivo. In vitro, TCDD did not consistently increase the percentage of CD19+CD24+CD38+ cells using splenocytes, purified B cells or bone marrow (BM) cells. However, TCDD increased IL-10 in all three culture preparations, and TCDD increased the percentage of CD5+CD24+CD38+ cells producing IL-10. In EAE, TCDD did not affect the percentage of the CD24+CD38+ cell population in CD19, B220 or CD5 B cells in splenocytes (SPLC), lymph nodes (LN) nor BM cells at end-stage disease. On the other hand, TCDD increased the CD19+CD24+CD38+ percentage in the spinal cord (SC) in EAE. Moreover, TCDD-treated B cells isolated from spleens or TCDD-treated BM cells in EAE mice modestly reduced the ability of naïve effector T cells to express interferon (IFN)-γ and tumor necrosis factor (TNF)-α. Together these data show that TCDD can induce regulatory functions in B cells, although it was not obvious simply by examining the expression of regulatory markers but by assessing function by cytokine production or mixed lymphocyte responses.
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