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Contactin-1 Is Required for Peripheral Innervation and Immune Homeostasis Within the Intestinal Mucosa.
Frontiers in Immunology ( IF 5.7 ) Pub Date : 2020-05-19 , DOI: 10.3389/fimmu.2020.01268
Marisol Veny 1 , Daniela Grases 2 , Karolina Kucharova 1 , Wai Wai Lin 1 , Jennifer Nguyen 1 , Sarah Huang 1 , Carl F Ware 1 , Barbara Ranscht 2 , John R Šedý 1
Affiliation  

Neuronal regulation of diverse physiological functions requires complex molecular interactions in innervated tissues to maintain proper organ function. Here we show that loss of the neuronal cell surface adhesion/recognition molecule Contactin-1 (Cntn1) directly impairs intestinal function causing wasting that subsequently results in global immune defects. Loss of Cntn1 results in hematologic alterations and changes in blood metabolites associated with malnourishment. We found thymus and spleen of Cntn1-deficient animals atrophied with severe reductions in lymphocyte populations. Elevated thymic Gilz expression indicated ongoing glucocorticoid signaling in Cntn1-deficient animals, consistent with the malnourishment phenotype. Intestinal Contactin-1 was localized to neurons in the villi and the submucosal/myenteric plexus that innervates smooth muscle. Loss of Cntn1 was associated with reduced intestinal Bdnf and Adrb2, indicating reduced neuromuscular crosstalk. Additionally, loss of Cntn1 resulted in reduced recruitment of CD3+ T cells to villi within the small intestine. Together, these data illustrate the critical role of Contactin-1 function within the gut, and how this is required for normal systemic immune functions.



中文翻译:

Contactin-1 是肠道粘膜内外周神经支配和免疫稳态所必需的。

多种生理功能的神经元调节需要神经支配组织中复杂的分子相互作用以维持适当的器官功能。在这里,我们表明神经元细胞表面粘附/识别分子 Contactin-1 的丧失(cntn1)直接损害肠道功能,导致消瘦,随后导致全球免疫缺陷。损失cntn1导致与营养不良相关的血液学改变和血液代谢物的变化。我们发现胸腺和脾脏cntn1- 有缺陷的动物因淋巴细胞数量严重减少而萎缩。胸腺升高吉尔兹 表达表明正在进行的糖皮质激素信号传导 cntn1-缺陷动物,与营养不良表型一致。Intestinal Contactin-1 定位于绒毛中的神经元和支配平滑肌的粘膜下/肌间丛。损失cntn1 与肠道减少有关 BdnfAdrb2,表明神经肌肉串扰减少。此外,损失cntn1导致 CD3 + T 细胞向小肠绒毛的募集减少。总之,这些数据说明了 Contactin-1 功能在肠道内的关键作用,以及正常的全身免疫功能如何需要它。

更新日期:2020-06-26
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