{"title":"Fecal CD200 as a Measure of Immunosuppressive CD200L and Proinflammatory CD200S at the Feto-Maternal Interface","authors":"David A. Clark, Paul Moayyedi","doi":"10.1111/aji.70120","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Problem</h3>\n \n <p>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<sup>+</sup> NK cells releasing proinflammatory CD200S<sup>+</sup> granules. We asked if subnormal epithelial CD200L was associated with increased degranulation of stromal CD200<sup>+</sup>CD56<sup>+</sup>NK cells. Systemic effects would include an augmented proinflammatory milieu at the feto-maternal decidual interface.</p>\n </section>\n \n <section>\n \n <h3> Methods of Study</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Epithelium and underlying stroma showed CD200L<sup>+</sup> cells, CD200S<sup>+</sup> cells, and CD56<sup>+</sup> cells releasing CD200S-positive granules. As epithelial CD200L expression decreased, the proportion of the degranulating CD56<sup>+</sup> 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.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Decreased epithelial CD200L increased both CD66<sup>+</sup> CD200S<sup>+</sup> stromal cells and their degranulation. This implies potential functional effects. Stool CD200 may reflect the level of CD200 at the feto-maternal decidual interface.</p>\n </section>\n </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 1","pages":""},"PeriodicalIF":2.5000,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70120","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Reproductive Immunology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/aji.70120","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
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.
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.