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Endogenous Transforming Growth Factor‐ β Inhibits Toll‐Like Receptor Mediated Activation of Human Uterine Natural Killer Cells
Author(s) -
Eriksson Mikael,
Meadows Sarah K.,
Wira Charles R.,
Sentman Charles L.
Publication year - 2006
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/j.1600-0897.2006.00432.x
Subject(s) - cytokine , tlr2 , biology , endocrinology , receptor , transforming growth factor beta , medicine , toll like receptor , endometrium , innate immune system , immune system , transforming growth factor , microbiology and biotechnology , immunology , biochemistry
Problem 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)‐ β in human endometrium. Method of study Single cells were isolated from human endometrium, and interferon (IFN)‐ γ production by endometrium cells and uNK cells was determined after stimulation by TLR agonists. The role of TGF‐ β in regulating this response was tested by blocking TGF‐ β function using antibodies or a specific inhibitor, SB431542. Results TGF‐ β blockade increased TLR agonist induced IFN‐ γ 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‐ β or TGF‐ β receptor signaling had no effect on constitutive cytokine production in the absence of TLR agonists. Conclusion The results indicate that endogenous TGF‐ β 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‐ β present within the human endometrium.