Endogenous transforming growth factor-beta inhibits toll-like receptor mediated activation of human uterine natural killer cells.
OBJECTIVE
Toll-like receptors (TLRs) recognition is an important means for the innate immune system to rapidly respond to pathogen invasion. Our aim was to determine whether uterine natural killer (uNK) cell cytokine production induced by stimulation through TLRs could be regulated by endogenous transforming growth factor (TGF)-beta in human endometrium.


METHODS
Single cells were isolated from human endometrium, and interferon (IFN)-gamma production by endometrium cells and uNK cells was determined after stimulation by TLR agonists. The role of TGF-beta in regulating this response was tested by blocking TGF-beta function using antibodies or a specific inhibitor, SB431542.


RESULTS
TGF-beta blockade increased TLR agonist induced IFN-gamma by uNK cells. The regulation of uNK cell cytokine production was observed when uNK cells were incubated with agonists for TLR2 (PGN) or TLR3 (polyI:C). Blockade of TGF-beta or TGF-beta receptor signaling had no effect on constitutive cytokine production in the absence of TLR agonists.


CONCLUSIONS
The results indicate that endogenous TGF-beta alters cytokine responses of uNK cells in human endometrium in response to TLR agonists. These data suggest that uNK cell responses to microbial pathogens in the endometrium are regulated by the amount of biologically active TGF-beta present within the human endometrium.
Eriksson
Mikael
M
Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA.
Meadows
Sarah K
SK
Wira
Charles R
CR
Sentman
Charles L
CL
D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000819:agonists / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014599:Uterus / Q000276:immunology* / Q000378:metabolism*
D016207:Cytokines; D018125:Receptors, Transforming Growth Factor beta; D051193:Toll-Like Receptors; D016212:Transforming Growth Factor beta