The role of Foxp3+ regulatory T-cells in endometriosis: a potential controlling mechanism for a complex, chronic immunological condition.
BACKGROUND
Endometriosis is an inflammatory condition, associated with highly dysregulated immune response at both uterine and peritoneal levels. Surprisingly, Foxp3+ regulatory T-cells, which control and suppress a range of immune responses, have not previously been investigated in endometriosis.


RESULTS
Immunohistochemical analysis of Foxp3+ cells in 127 eutopic endometrial samples and 59 ectopic peritoneal lesions revealed that these immune cell populations are highly disturbed in women suffering from endometriosis. We showed that Foxp3+ cells remained highly up-regulated during the secretory phase of the menstrual cycle, while at this time their expression is significantly down-regulated in women without endometriosis (P < 0.001). Foxp3+ cells were detected in the stroma of 18 of the 59 peritoneal endometriotic lesions, but not in the surrounding or control peritoneal tissue.


CONCLUSIONS
We propose that in eutopic endometrium in women with endometriosis Foxp3+ cells decrease the ability of newly recruited immune cell populations to effectively recognize and target endometrial antigens shed during menstruation, allowing their survival and ability to implant in ectopic sites. At these ectopic sites, variable expression of Foxp3+ cells within some peritoneal endometriotic lesions is likely to be linked to the characteristics and stage of individual lesion development and be playing key roles in pathogenesis and progression of this unique condition.
Berbic
Marina
M
Department of Obstetrics and Gynaecology, Queen Elizabeth II Research Institute for Mothers and Infants, the University of Sydney, New South Wales, Australia. m.berbic@usyd.edu.au
Hey-Cunningham
Alison J
AJ
Ng
Cecilia
C
Tokushige
Natsuko
N
Ganewatta
Subha
S
Markham
Robert
R
Russell
Peter
P
Fraser
Ian S
IS
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D004715:Endometriosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008597:Menstrual Cycle / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D010532:Peritoneal Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010537:Peritoneum / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors