title: The placental immunomodulatory cytokine regeneration and tolerance factor is also expressed by both human cycling and early pregnant endometrium.
abstract: OBJECTIVE
  Regeneration and tolerance factor (RTF) has been recently suggested to contribute to the control of fetal-ablating immunity at the maternal-fetal interface through the induction of T helper 2 (Th2)-dominated response. The protein consists of a membrane-associated 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-hematopoietic 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.
  
  
  METHODS
  The 20 kDa 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-polymerase chain reaction.
  
  
  RESULTS
  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-endometrial stromal cells when compared to proliferative phase samples. Inflammatory cytokines, interleukin-1beta and tumour necrosis factor alpha were able to directly increase endometrial RTF mRNA expression.
  
  
  CONCLUSIONS
  These results indicate that RTF is constitutively expressed at endometrial and decidual level and its up-regulation during the secretory phase of the cycle may be relevant in mediating some immune-related aspects of uterine physiology.
authors.affiliation: II Department of Obstetrics and Gynecology, University of Milano, Milano, Italy.
authors.forename: Debora
authors.initials: D
authors.lastname: Lattuada
authors.forename: Silvia
authors.initials: S
authors.lastname: Mangioni
authors.forename: Paola
authors.initials: P
authors.lastname: Viganò
authors.forename: Evangelos I
authors.initials: EI
authors.lastname: Ntrivalas
authors.forename: Margherita
authors.initials: M
authors.lastname: Rossi
authors.forename: Francesco
authors.initials: F
authors.lastname: Palotti
authors.forename: Silvestro
authors.initials: S
authors.lastname: Carinelli
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Beaman
authors.forename: Anna M
authors.initials: AM
authors.lastname: Di Blasio
mesh_terms: D002453:Cell Cycle; D002478:Cells, Cultured; D004717:Endometrium / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D010920:Placenta / Q000166:cytology* / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013491:Suppressor Factors, Immunologic / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors; D006180:Proton-Translocating ATPases
chemical_list: D012333:RNA, Messenger; D013491:Suppressor Factors, Immunologic; C525845:ATP6V0A2 protein, human; D006180:Proton-Translocating ATPases