1 / 16

Division of Genetic and Cell Biology Chromatin Dynamics lab

Myeloid-Derived Suppressor Cells as A Potential Therapuetic Target For Women With Early Pregnancy Loss. Rohini R Nair Marie Curie-COFUND fellow. Division of Genetic and Cell Biology Chromatin Dynamics lab University of San Raffaele, Milan, Italy. Inflammation. Acute Inflammation

gcorriveau
Download Presentation

Division of Genetic and Cell Biology Chromatin Dynamics lab

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Myeloid-Derived Suppressor Cells as A Potential Therapuetic Target For Women With Early Pregnancy Loss Rohini R Nair Marie Curie-COFUND fellow Division of Genetic and Cell Biology Chromatin Dynamics lab University of San Raffaele, Milan, Italy

  2. Inflammation Acute Inflammation Chronic Inflammation

  3. Inflammatory State Inflammatory state during pregnancy Quiescent State I D G I – Implantation, G – Gestation, D - Delivery

  4. Prognosis of pregnancy Teklenburg et al., 2010

  5. S100A8 & S100A9

  6. Role of S100A8 & S100A9 pregnancy loss In Endometrium Maternal tissue In Chorionic villi Fetal tissue Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) of S100A8 & S100A9 in endometrial deciduas and chorionic villi

  7. S100A8 S100A9 Quantitative real time PCR of S100A8 & S100A9 in endometrial deciduas and chorionic villi S100A8 S100A9 Western blot analysis of S100A8 & S100A9 in endometrial deciduas and chorionic villi

  8. S100A8 cytokine levels in peripheral blood S100A8 level remain high during 7th day of menstrual cycle compared to 21st day of menstrual cycle. Serum from five healthy volunteers in proliferative (7th day LMP) and secretory phase (21st day LMP) of menstrual cycle were collected. S100A8 levels were analyzed through ELISA assay. Bar diagram representing S100A8 level (pg/ml) in proliferative (7th day of LMP) and secretory phase (21st day of LMP) of menstrual cycle (A). S100A8 levels did not change in 1st, 2nd and 3rd trimester of pregnancy. Bar diagram representing 1st (n=10), 2nd (n=7) and 3rd (n=5) trimester of pregnancy (B). S100A8 levels were found to be elevated in early pregnancy loss patients compared to healthy controls. Bar diagram representing controls (n=10) and EPL cases (n=10) * represents p<0.01 (C).

  9. Myeloid derived Suppressor Cells

  10. Level of Myeloid derived suppressor cells (MDSC) in menstrual cycle and pregnancy Mean Fluorescence Intensity of Cd11b 7th day of LMP 15 23.05 11.20 26.48 11.10 21st day of LMP 10 % CD11b+CD33+ cells in blood P=0.02 CD11b 0.14 0.07 5 0 7th day 21st day CD33 1st Trimester 2nd Trimester 3rd Trimester 18.5 17.5 17 12 5.83 4 CD11b 0.30 0.87 0.30 CD33 *** 15 *** 10 % CD11b+CD33+ cells in blood 5 0 21st day 1st Trimester 2nd Trimester 3rd Trimester

  11. 21st Day MDSC Uterine epithelium MDSC MDSC MDSC MDSC MDSC MDSC MDSC MDSC MDSC MDSC Treg 7th Day 1st trimester 3rd trimester MDSC Treg Treg Tolerance of Embryo at Implantation stage Treg Loss of Tolerance i.e. Parturition

  12. Level and suppressive function of MDSC in early pregnancy loss Pregnant Females in 1st trimester Early Pregnancy Loss patients 15 18.5 17.5 20.77 4.32 ** 10 % CD11b+CD33+ cells in blood CD11b 5 0.87 0.23 0 Controls EPL CD33 5 25 * * 4 20 IL-2 (pg/ml) 3 Absorbance (570nm) 15 2 10 1 5 0 0 Undepleted CD33 depleted Undepleted CD33 depleted 0.8 0.6 * 0.6 undepleted / CD33 depleted Absorbance (570nm) undepleted / CD33 depleted IL-2 (pg/ml) 0.4 0.4 0.2 0.2 0.0 0.0 Controls EPL Controls EPL

  13. MDSC level in Implantation Site CD33+ cells in endometrium Controls EPL ** 15 10 Average No of CD33+ cells Reduced CD11b+CD33+ MDSC correlate negatively with the increases S100A8 level in peripheral blood of Recurrent Early Pregnancy loss (RPL) patients. 5 0 Controls EPL

  14. Myeloid-Derived Suppressor Cells can be used as a Potential Therapuetic Target For Women With Early Miscarriage

  15. Acknowledgement • Patients and volunteers for providing blood samples and tissue samples. • This work was financially supported by the Department of Biotechnology, New Delhi, India. • I would also acknowledge the help from DST-Confocal facility in BHU for confocal microscopy and Interdisciplinary School of Life Science for BD FACS calibur.

  16. Reproductive Genetic Group Thank You Chromatin Dynamic Group

More Related