Fecal CD200 as a Measure of Immunosuppressive CD200L and Proinflammatory CD200S at the Feto-Maternal Interface

IF 2.5 3区 医学 Q3 IMMUNOLOGY
David A. Clark, Paul Moayyedi
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引用次数: 0

Abstract

Problem

Patients with diarrhea-predominant irritable bowel syndrome have an increased risk of recurrent miscarriage (RM). Loss of chromosomally normal post-implantation embryos is triggered by the proinflammatory cytokines interferon-γ and TNF-α from NK cells and macrophages. Mouse models of RM similar to human unexplained RM have implicated fecal LPS as an important abortifacient. However, subnormal expression of immunosuppressive CD200L at the feto-maternal interface has also been implicated in RM. Human stool contains desquamated epithelium expressing immunosuppressive CD200L and stromal CD56+ NK cells releasing proinflammatory CD200S+ granules. We asked if subnormal epithelial CD200L was associated with increased degranulation of stromal CD200+CD56+NK cells. Systemic effects would include an augmented proinflammatory milieu at the feto-maternal decidual interface.

Methods of Study

Quantitative analysis of biopsies of proximal and distal colon for immunostained for CD200L, CD200S, and CD56-positive cells. CD200 ELISA Assay of stool extracts was done.

Results

Epithelium and underlying stroma showed CD200L+ cells, CD200S+ cells, and CD56+ cells releasing CD200S-positive granules. As epithelial CD200L expression decreased, the proportion of the degranulating CD56+ cells significantly increased. Degranulation was significantly greater in irritable bowel syndrome, diarrhea predominant subtype (IBS-D) cases compared to controls. CD200L was detected in stool extracts.

Conclusions

Decreased epithelial CD200L increased both CD66+ CD200S+ stromal cells and their degranulation. This implies potential functional effects. Stool CD200 may reflect the level of CD200 at the feto-maternal decidual interface.

Abstract Image

粪便CD200作为免疫抑制CD200L和促炎性CD200S在胎母界面的测量
问题腹泻为主的肠易激综合征患者有复发性流产(RM)的风险增加。来自NK细胞和巨噬细胞的促炎细胞因子干扰素-γ和TNF-α触发了胚胎着床后染色体正常胚胎的丢失。小鼠RM模型与人类不明原因RM相似,表明粪便LPS是一种重要的流产剂。然而,免疫抑制CD200L在胎母界面的亚正常表达也与RM有关。人的粪便含有脱皮上皮,表达免疫抑制CD200L和间质CD56+ NK细胞,释放促炎CD200S+颗粒。我们询问上皮细胞CD200L亚正常是否与间质CD200+CD56+NK细胞脱颗粒增加有关。全身性影响包括在胎儿-母体蜕膜界面增强促炎环境。研究方法对结肠近端和远端活检组织进行CD200L、CD200S和cd56阳性细胞的免疫染色定量分析。采用CD200酶联免疫吸附试验对粪便提取物进行检测。结果上皮及下层基质显示CD200L+细胞、CD200S+细胞和CD56+细胞释放CD200S阳性颗粒。随着上皮细胞CD200L表达的降低,脱颗粒细胞CD56+的比例显著增加。与对照组相比,肠易激综合征,腹泻主要亚型(IBS-D)病例的脱颗粒明显更大。粪便提取物中检测到CD200L。结论上皮细胞CD200L的降低使CD66+ CD200S+间质细胞及其脱颗粒增多。这意味着潜在的功能影响。粪便CD200可反映胎母个体界面的CD200水平。
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来源期刊
CiteScore
6.20
自引率
5.60%
发文量
314
审稿时长
2 months
期刊介绍: The American Journal of Reproductive Immunology is an international journal devoted to the presentation of current information in all areas relating to Reproductive Immunology. The journal is directed toward both the basic scientist and the clinician, covering the whole process of reproduction as affected by immunological processes. The journal covers a variety of subspecialty topics, including fertility immunology, pregnancy immunology, immunogenetics, mucosal immunology, immunocontraception, endometriosis, abortion, tumor immunology of the reproductive tract, autoantibodies, infectious disease of the reproductive tract, and technical news.
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