TCDD Inhibition of IgG1 Production in Experimental Autoimmune Encephalomyelitis (EAE) and In Vitro.
TCDD Inhibition of IgG1 Production in Experimental Autoimmune Encephalomyelitis (EAE) and In Vitro.
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DOI：
10.3390/antib11010004
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发表时间：
2022-01-09
期刊：
影响因子：
--
通讯作者：
Kaplan BLF
中科院分区：
文献类型：
--
作者：
Nicaise AJ;McDonald A;Sears ER;Sturgis T;Kaplan BLF
环境污染物2，3，7，8-四氯二苯并对二恶英(TCDD)是芳烃受体(AhR)的配体。TCDD具有免疫毒性的特点，包括抑制抗体的产生。先前我们在实验性自身免疫性脑脊髓炎(EAE)模型中发现TCDD能抑制髓鞘少突胶质细胞糖蛋白(MOG)多肽特异性免疫球蛋白和减轻疾病。因此，这项研究的目的是表征TCDD对EAE和体外培养的Ig G亚类的影响，并评估对不同组织来源的B细胞的影响。TCDD可适度抑制脾细胞(SPLC)细胞内免疫球蛋白的表达，但对骨髓(BM)和淋巴结(LN)细胞内的免疫球蛋白表达无明显影响。为了进一步了解TCDD对免疫球蛋白的影响，我们在体外分别用内毒素和内毒素+IL-4刺激IgG3和IgG1的产生。TCDD优先抑制IgG1+细胞表面的表达，特别是在SPLC。TCDD能抑制SPLC和B细胞分泌IgG1和IgG3，但不能抑制BM细胞分泌IgG1和IgG3。最后，我们重新研究了EAE模型，并确定TCDD抑制了MOG特异性IgG1的产生。综上所述，这些数据表明，免疫球蛋白IgG1亚类是TCDD抑制的敏感靶点。EAE的部分病理生理学涉及产生致病抗体，这种抗体可以招募细胞溶解细胞来摧毁组成髓鞘的表达MOG的细胞，因此抑制IgG1可能有助于TCDD的EAE疾病的缓解。
The environmental contaminant 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) is a ligand for the aryl hydrocarbon receptor (AhR). TCDD is well-characterized to produce immunotoxicity, including suppression of antibody production. Previously we showed that TCDD inhibited myelin oligodendrocyte glycoprotein (MOG) peptide-specific IgG and attenuated disease in experimental autoimmune encephalomyelitis (EAE) model in mice. Thus, the purpose of this study was to characterize the effects of TCDD on IgG subclasses in EAE and in vitro and assess effects in B cells derived from various tissues. TCDD modestly suppressed intracellular IgG expression in splenocytes (SPLC), but not bone marrow (BM) or lymph node (LN) cells. To further understand TCDD’s effects on IgG, we utilized LPS and LPS + IL-4 in vitro to stimulate IgG3 and IgG1 production, respectively. TCDD preferentially suppressed IgG1+ cell surface expression, especially in SPLC. However, TCDD was able to suppress IgG1 and IgG3 secretion from SPLC and B cells, but not BM cells. Lastly, we revisited the EAE model and determined that TCDD suppressed MOG-specific IgG1 production. Together these data show that the IgG1 subclass of IgG is a sensitive target of suppression by TCDD. Part of the pathophysiology of EAE involves production of pathogenic antibodies that can recruit cytolytic cells to destroy MOG-expressing cells that comprise myelin, so inhibition of IgG1 likely contributes to TCDD’s EAE disease attenuation.
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影响因子：
4.5
作者：
Kummari E;Rushing E;Nicaise A;McDonald A;Kaplan BLF
通讯作者：
Kaplan BLF
影响因子：
2
作者：
Kim, HA;Kim, EM;Heo, Y
通讯作者：
Heo, Y
影响因子：
4.5
作者：
Nohara, K;Fujimaki, H;Tohyama, C
通讯作者：
Tohyama, C
影响因子：
3.5
作者：
KARRAS, JG;CONRAD, DH;HOLSAPPLE, MP
通讯作者：
HOLSAPPLE, MP
影响因子：
3.8
作者：
Salisbury, Richard L.;Sulentic, Courtney E. W.
通讯作者：
Sulentic, Courtney E. W.