Increased Monocyte Production of IL-6 after Toll-like Receptor Activation in Children with Autism Spectrum Disorder (ASD) Is Associated with Repetitive and Restricted Behaviors.
Increased Monocyte Production of IL-6 after Toll-like Receptor Activation in Children with Autism Spectrum Disorder (ASD) Is Associated with Repetitive and Restricted Behaviors.
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DOI：
10.3390/brainsci12020220
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发表时间：
2022-02-05
期刊：
影响因子：
3.3
通讯作者：
Ashwood P
中科院分区：
文献类型：
--
作者：
Hughes HK;Onore CE;Careaga M;Rogers SJ;Ashwood P
自闭症谱系障碍(ASD)的患病率急剧上升，引发了对ASD危险因素的研究。这项研究确定了ASD的免疫风险因素，以及自闭症患者经常经历的免疫功能障碍和过度炎症的证据。包括IL-6在内的先天炎性细胞因子的增加在ASD中反复可见；然而，ASD中IL-6过多的原因尚未确定。在这里，我们探索自闭症儿童循环单核细胞的特异性反应。我们从全血中分离CD14+单核细胞，在单独介质、脂磷壁酸激活TLR2和内毒素激活TLR4三种条件下刺激它们24小时。然后，我们使用人类多重珠状免疫分析法测量了细胞上清液中分泌的细胞因子浓度。我们发现，在TLR4激活后，自闭症儿童CD14+单核细胞产生的IL-6比发育正常儿童的单核细胞高。IL-6浓度也与限制性和重复性行为的恶化有关。这些发现表明髓系细胞的激活功能障碍，并可能表明这一谱系的其他细胞，包括脑中的巨噬细胞和小胶质细胞，可能也有类似的功能障碍。ASD中髓系细胞的进一步研究是有必要的。
The prevalence of autism spectrum disorder (ASD) has starkly increased, instigating research into risk factors for ASD. This research has identified immune risk factors for ASD, along with evidence of immune dysfunction and excess inflammation frequently experienced by autistic individuals. Increased innate inflammatory cytokines, including interleukin (IL)-6, are seen repeatedly in ASD; however, the origin of excess IL-6 in ASD has not been identified. Here we explore specific responses of circulating monocytes from autistic children. We isolated CD14+ monocytes from whole blood and stimulated them for 24 h under three conditions: media alone, lipoteichoic acid to activate TLR2, and lipopolysaccharide to activate TLR4. We then measured secreted cytokine concentrations in cellular supernatant using a human multiplex bead immunoassay. We found that after TLR4 activation, CD14+ monocytes from autistic children produce increased IL-6 compared to monocytes from children with typical development. IL-6 concentration also correlated with worsening restrictive and repetitive behaviors. These findings suggest dysfunctional activation of myeloid cells, and may indicate that other cells of this lineage, including macrophages, and microglia in the brain, might have a similar dysfunction. Further research on myeloid cells in ASD is warranted.
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自闭症谱系障碍（ASD）、精神分裂症和双相情感障碍中全转录组异构体水平失调
影响因子：
56.9
作者：
Gandal, Michael J.;Zhang, Pan;Geschwind, Daniel H.
通讯作者：
Geschwind, Daniel H.
DOI：
10.1126/science.aag3194
发表时间：
2016-08-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Estes ML;McAllister AK
通讯作者：
McAllister AK
影响因子：
15.1
作者：
Enstrom, Amanda M.;Onore, Charity E.;de Water, Judy A. Van;Ashwood, Paul
通讯作者：
Ashwood, Paul
DOI：
10.15585/mmwr.ss6706a1
发表时间：
2018-04-27
期刊：
Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)
影响因子：
--
作者：
Baio J;Wiggins L;Christensen DL;Maenner MJ;Daniels J;Warren Z;Kurzius-Spencer M;Zahorodny W;Robinson Rosenberg C;White T;Durkin MS;Imm P;Nikolaou L;Yeargin-Allsopp M;Lee LC;Harrington R;Lopez M;Fitzgerald RT;Hewitt A;Pettygrove S;Constantino JN;Vehorn A;Shenouda J;Hall-Lande J;Van Naarden Braun K;Dowling NF
通讯作者：
Dowling NF
影响因子：
11.2
作者：
Campbell, Daniel B.;D'Oronzio, Rosanna;Persico, Antonio M.
通讯作者：
Persico, Antonio M.