Amniotic membrane extract differentially regulates human peripheral blood T cell subsets, monocyte subpopulations and myeloid dendritic cells

Abstract

The discovery of the immunoregulatory potential of human amniotic membrane (hAM) propelled several studies focusing on its application for the treatment of immunological disorders. However, there is little information regarding the effects of hAM on distinct activation and differentiation stages of immune cells. Here, we aim to investigate the effect of human amniotic membrane extract (hAME) on the pattern of cytokine production by T cells, monocytes and myeloid dendritic cells (mDCs). For this purpose, peripheral blood mononuclear cells (PBMCs) from eight healthy individuals were stimulated in vitro in the presence or absence of hAME. Mitogen-induced proliferation of PBMCs and cytokine production among the distinct T cell functional compartments, monocyte subpopulations and mDCs were evaluated. hAME displayed an anti-proliferative effect and decreased the frequency of T cells producing tumor necrosis factor (TNF)α, interferon (IFN)γ and interleukin (IL)-2, for all T cell functional compartments. The frequency of IL-17 and IL-9-producing T cells was also reduced. The inhibition of mRNA expression of granzyme B, perforin and NKG2D by CD8 T cells and γδ T cells and the augment of FoxP3 and IL-10 in CD4 T cells and IL-10 in regulatory T cells were also observed. Furthermore, hAME inhibited IFNγ-induced protein (IP)-10 expression by classical and non-classical monocytes, without hampering the production of TNFα and IL-6 by monocytes and mDCs. These results suggest that hAME exerts an anti-inflammatory effect on T cells, still at a different extent for distinct T cell functional compartments.

Human Amniotic Epithelial Cells Affect the Functions of Neutrophils

“…In the case of phagocytosis, of note, by decreasing the ratio of HAECs：neutrophils, the phagocytic activity increased, as we observed the lowest and highest level of phagocytosis, respectively at the highest and lowest ratio of HAECs to neutrophils. These incompatible findings may be due to the fact that HAECs differentially regulate different populations of immune cells as it has been presented recently (26,27).…”

“…The present dominant view of HAECs is that they are immunomodulatory cells which express or secrete surface/soluble immunoreactive molecules ( 10 , 27 , 28 ). Some of these molecules such as HLA-G ( 29 ), PGE2 ( 30 , 31 ), IL-10 ( 32 ), and IDO ( 33 ) have already been shown that can influence neutrophils as well.…”

Amniotic membrane transplantation for infectious keratitis: a systematic review and meta-analysis

“…Second, studies have shown that AM could serve as an effective antibiotic reservoir when used in combination with antibiotics and provide sustained drug delivery 60 . Furthermore, AM has been shown to exhibit anti-inflammatory function via regulation of T-cell function and secretion of anti-inflammatory antagonists, including IL-1ra, sTNF, and VEGF-R 61 , 62 . This anti-inflammatory property will have a long-term beneficial effect on the cornea, hence vision, as persistent corneal vascularization could negatively affect the vision, either directly via encroachment on the visual axis or indirectly via lipid keratopathy where exudation of lipid and inflammatory cells extends to the visual axis 63 .…”

Leveraging bioengineering to assess cellular functions and communication within human fetal membranes

“…Blockade of PGE2 production in DSCs rescued TNFα production, indicating that DSCs suppress Mφ TNFα production via PGE2. Conditioned media from amniotic membranes was added to peripheral blood immune cell subsets and responses characterized [94] and found that while T cells were skewed towards Th2 responses, blood monocytes exhibited CXCL10 suppression but no change to levels of TNF or IL-6. Use of activated or resting Mφ-conditioned media on CTBs of the fetal membranes induced changes in gene expression in leukocyte trafficking, adhesion, and cytokinerelated genes, all of which was independent of changes to DNA methylation and thus likely not due to epigenetic regulation [95].…”