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Goblet cell associated antigen passages support the induction and maintenance of oral tolerance.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2019-12-09 , DOI: 10.1038/s41385-019-0240-7
Devesha H Kulkarni 1 , Jenny K Gustafsson 1 , Kathryn A Knoop 1 , Keely G McDonald 1 , Shay S Bidani 1 , Jazmyne E Davis 1 , Alexandria N Floyd 1 , Simon P Hogan 2 , Chyi-Song Hsieh 1 , Rodney D Newberry 1
Affiliation  

Tolerance to innocuous antigens from the diet and the commensal microbiota is a fundamental process essential to health. Why tolerance is efficiently induced to substances arising from the hostile environment of the gut lumen is incompletely understood but may be related to how these antigens are encountered by the immune system. We observed that goblet cell associated antigen passages (GAPs), but not other pathways of luminal antigen capture, correlated with the acquisition of luminal substances by lamina propria (LP) antigen presenting cells (APCs) and with the sites of tolerance induction to luminal antigens. Strikingly this role extended beyond antigen delivery. The GAP function of goblet cells facilitated maintenance of pre-existing LP T regulatory cells (Tregs), imprinting LP-dendritic cells with tolerogenic properties, and facilitating LP macrophages to produce the immunomodulatory cytokine IL-10. Moreover, tolerance to dietary antigen was impaired in the absence of GAPs. Thus, by delivering luminal antigens, maintaining pre-existing LP Tregs, and imprinting tolerogenic properties on LP-APCs GAPs support tolerance to substances encountered in the hostile environment of the gut lumen.

中文翻译:

杯状细胞相关抗原传代支持口服耐受的诱导和维持。

对饮食和共生微生物群中无害抗原的耐受性是健康所必需的基本过程。为什么能够有效地诱导对肠腔恶劣环境产生的物质的耐受性尚不完全清楚,但可能与免疫系统如何遇到这些抗原有关。我们观察到,杯状细胞相关抗原通道(GAP),而不是其他管腔抗原捕获途径,与固有层(LP)抗原呈递细胞(APC)对管腔物质的获取以及对管腔抗原的耐受诱导位点相关。 。引人注目的是,这种作用超出了抗原递送的范围。杯状细胞的 GAP 功能有助于维持预先存在的 LP T 调节细胞 (Treg),使 LP 树突状细胞具有耐受性,并促进 LP 巨噬细胞产生免疫调节细胞因子 IL-10。此外,在缺乏 GAP 的情况下,对饮食抗原的耐受性也会受到损害。因此,通过递送管腔抗原、维持预先存在的 LP Tregs 以及在 LP-APC 上印记致耐受特性,GAP 支持对肠腔恶劣环境中遇到的物质的耐受性。
更新日期:2019-12-09
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