A paired investigation of endometrial and peripheral dendritic cell subpopulations: Impaired antigen presentation in women with endometriosis?  — ASN Events

A paired investigation of endometrial and peripheral dendritic cell subpopulations: Impaired antigen presentation in women with endometriosis?  (#289)

Cecilia Wong 1 , Azmat Riaz 1 , Marina Berbic 1 , Philip D. Fromm 2 , Fiona Kupersanin 2 , Derek N.J. Hart 2 , Uli Schmidt 3 , Robert P.S Jansen 3 , Robert Markham 1 , Ian S. Fraser 1 , Alison J. Hey-Cunningham 1
  1. The Queen Elizabeth II Research Institute for Mothers and Infants, Obstetrics, Gynaecology and Neonatology, University of Sydney, Sydney, NSW, Australia
  2. Dendritic Cell Biology and Therapeutics Group, ANZAC Research Institute, The University of Sydney, Sydney, NSW, Australia
  3. Genea Limited, Sydney, NSW, Australia

Background:

Endometrial dendritic cells (DCs) play important roles in protection from pathogens, regulating endometrial changes during the menstrual cycle, and preparation for implantation [1, 2]. DCs are a heterogeneous population of immune cells that are crucial for initiating and regulating both innate and adaptive immune responses [3]. Human blood and tissues contain two main DC subtypes, myeloid (mDC) and plasmacytoid (pDC). Dysregulations of endometrial DCs are implicated in endometriosis and other reproductive pathologies such as recurrent miscarriage [4]. However, detailed knowledge of changes in different endometrial DC subpopulations is lacking.

Objective:

To comprehensively characterise DC subpopulations in the endometrium of women of reproductive age based on the current international consensus on DC nomenclature.

Methods:

Matched endometrial and peripheral blood samples were obtained (n = 9). Multi-colour flow cytometry analysis was performed. DCs were identified by their lack of expression of common lineage markers (CD3,14,19,20,56), and positive expression of HLA-DR. Three CD11c+ mDC (CD1c+, CD141+, CD16+) and two CD 11c-CD304+ pDC (CD11cCD2- and CD11cCD2+) populations were investigated.

Results:

All three mDC and both pDC subsets were present in the endometrium. Preliminary results show higher proportions of CD11c+ mDC than CD304+ pDC in the endometrium (33.2±12.6% and 21.8±20.7% of Lin-HLADR+ cells, respectively). The large ranges observed in endometrial DC populations indicate a high degree of variation between women and during the menstrual cycle (mDC range=17.4-52.9% and pDC=0.1-53.2%). Our preliminary data suggest that mDCs peak during the secretory phase, whereas pDCs appear to peak during menstruation.

Conclusion:

A larger range of endometrial DC subpopulations have been characterised than has been previously investigated. The cyclical changes of both mDC and pDC indicate involvement in the signalling and functional changes of the uterus. Ongoing investigations are underway to more comprehensively characterise the DC populations during the normal menstrual cycle and in women with endometriosis. 

  1. 1. SCHULKE, L., MANCONI, F., MARKHAM, R. & FRASER, I. S. 2008. Endometrial dendritic cell populations during the normal menstrual cycle. Human Reproduction, 23, 1574-1580.
  2. 2. RIEGER, L., HONIG, A., SUTTERLIN, M., KAPP, M., DIETL, J., RUCK, P. & KAMMERER, U. 2004. Antigen presenting cells in human endometrium during the menstrual cycle compared to early pregnancy Journal of Society for Gynecologic Investigation, 11, 488-493.
  3. 3. GASIOROWSKI, R.E., JU, X., HART, D.N.J., CLARK, GEORGINA J.C. 2012. CD300 molecule regulation of human dendritic cell functions. Immunology Letters, 149, 93-100
  4. 4. SCHULKE, L., BERBIC, M., MANCONI, F., TOKUSHIGE, N., MARKHAM, R. & FRASER, I. S. 2009. Dendritic cell populations in the eutopic and ectopic endometrium of women with endometriosis. Human Reproduction, 24, 1695-1703.
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