Clark David A, Moayyedi Paul
Department of Medicine, Division of Clinical Immunology, Faculty of Health, Sciences HSC 3H2, McMaster University, Hamilton, Ontario, Canada.
Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Am J Reprod Immunol. 2025 Jul;94(1):e70120. doi: 10.1111/aji.70120.
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 CD200CD56NK cells. Systemic effects would include an augmented proinflammatory milieu at the feto-maternal decidual interface.
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.
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.
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.
腹泻型肠易激综合征患者复发性流产（RM）风险增加。植入后染色体正常胚胎的丢失是由自然杀伤细胞和巨噬细胞产生的促炎细胞因子干扰素-γ和肿瘤坏死因子-α引发的。与人类不明原因复发性流产相似的复发性流产小鼠模型表明粪便脂多糖是一种重要的堕胎因素。然而，免疫抑制性CD200L在母胎界面的表达低于正常水平也与复发性流产有关。人类粪便含有表达免疫抑制性CD200L的脱落上皮细胞和释放促炎CD200S颗粒的基质CD56自然杀伤细胞。我们询问上皮CD200L低于正常水平是否与基质CD200CD56自然杀伤细胞脱颗粒增加有关。全身影响将包括母胎蜕膜界面促炎环境增强。
对近端和远端结肠活检组织进行免疫染色，定量分析CD200L、CD200S和CD56阳性细胞。对粪便提取物进行CD200酶联免疫吸附测定。
上皮和下层基质显示有CD200L细胞、CD200S细胞和释放CD200S阳性颗粒的CD56细胞。随着上皮CD200L表达降低，脱颗粒CD56细胞的比例显著增加。与对照组相比，腹泻型肠易激综合征（IBS-D）病例的脱颗粒明显更严重。在粪便提取物中检测到CD200L。
上皮CD200L降低会增加CD66 CD200S基质细胞及其脱颗粒。这意味着可能存在功能影响。粪便CD200可能反映母胎蜕膜界面的CD200水平。
