{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T11:00:33Z","timestamp":1743159633126},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,9,16]],"date-time":"2004-09-16T00:00:00Z","timestamp":1095292800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2004,9]]},"abstract":"<jats:p><jats:bold>Problem:\u2002<\/jats:bold> Regeneration and tolerance factor (RTF) has been recently suggested to contribute to the control of fetal\u2010ablating immunity at the maternal\u2013fetal interface through the induction of T helper 2 (Th2)\u2010dominated response. The protein consists of a membrane\u2010associated domain and an extracellular portion which is proteolitically cleaved to yield a soluble peptide. In humans, it has been shown to be expressed by invading cytotrophoblasts and decidual lymphoid cells, to be increased on peripheral blood B lymphocytes during a normal gestation and on circulating natural killer cells during unsuccessful pregnancies. However, the expression of RTF in other cell types and, specifically, in non\u2010hematopoietic maternal cells of the human uterus has not been characterized in detail. Thus, we have specifically studied the expression and modulation of the cytokine in human endometrium obtained in different phases of the cycle and in early pregnancy.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> The 20\u2003kDa extracellular domain of RTF has been localized by immunohistochemical method and Western blot analysis. Levels of RTF messenger RNA (mRNA) in basal and stimulated conditions have been evaluated by semiquantitative reverse transcription\u2010polymerase chain reaction.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> The extracellular domain of RTF could be detected in both the glandular epithelium and stroma with diffuse distribution in both cycling endometrium and first trimester decidua. Both cycling and pregnant endometrium expressed the gene for RTF but mRNA levels resulted significantly increased in secretory phase\u2010endometrial stromal cells when compared to proliferative phase samples. Inflammatory cytokines, interleukin\u20101<jats:italic>\u03b2<\/jats:italic> and tumour necrosis factor <jats:italic>\u03b1<\/jats:italic> were able to directly increase endometrial RTF mRNA expression.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> These results indicate that RTF is constitutively expressed at endometrial and decidual level and its up\u2010regulation during the secretory phase of the cycle may be relevant in mediating some immune\u2010related aspects of uterine physiology.<\/jats:p>","DOI":"10.1111\/j.1600-0897.2004.00210.x","type":"journal-article","created":{"date-parts":[[2004,9,16]],"date-time":"2004-09-16T15:10:18Z","timestamp":1095347418000},"page":"224-231","source":"Crossref","is-referenced-by-count":8,"title":["The Placental Immunomodulatory Cytokine Regeneration and Tolerance Factor is also Expressed by Both Human Cycling and Early Pregnant 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