Journal Article

Stromal cells from perinatal and adult sources modulate the inflammatory immune response in vitro by decreasing Th1 cell proliferation and cytokine secretion

Khoury, Oula, Atala, Anthony, Murphy, Sean V.

2020

Overview

Many immune‐mediated conditions are associated with a dysregulated imbalance toward a Th1 response leading to disease onset, severity, and damage. Many of the therapies such as immunomodulators or anti‐TNF‐α antibodies often fall short in preventing disease progression and ameliorating disease conditions. Thus, new therapies that can target inflammatory environments would have a major impact in preventing the progression of inflammatory diseases. We investigated the role of human stromal cells derived from the amniotic fluid (AFSCs), the placenta (PLSCs), and bone marrow‐derived mesenchymal stromal cells (BM‐MSCs) in modulating the inflammatory response of in vitro‐stimulated circulating blood‐derived immune cells. Immune cells were isolated from the blood of healthy individuals and stimulated in vitro with antigens to activate inflammatory responses to stimuli. AFSC, BM‐MSCs, and PLSCs were cocultured with stimulated leukocytes, neutrophils, or lymphocytes. Inflammatory cytokine production, neutrophil migration, enzymatic degranulation, T cell proliferation, and subsets were evaluated. Coculture of all three stromal cell types decreased the gene expression of inflammatory cytokines and enzymes such as IL‐1β, IFN‐γ, TNF‐α, neutrophil elastase, and the transcription factor NF‐κB in lipopolysaccharide‐stimulated leukocytes. With isolated phytohemagglutinin‐stimulated peripheral blood mononuclear cells, cells coculture leads to a decrease in lymphocyte proliferation. This effect correlated with decreased numbers of Th1 lymphocytes and decreased secreted levels of IFN‐γ. Perinatal cells suppress the proliferation of Th1 cells and their associated cytokines.

• Publisher: John Wiley & Sons, Inc,Oxford University Press
• Subject: Amniotic fluid / Antigens / Blood / Bone marrow / Cell growth / Cell Proliferation / Cell‐based Drug Development, Screening, and Toxicology / Cytokines / Cytokines - metabolism / Degranulation / Disease / Elastase / Gene expression / Humans / Immune response / Immunomodulation / Immunomodulators / immunosuppression / Inflammation / Inflammation - immunology / Inflammatory diseases / Interferon / Leukocyte migration / Leukocytes (mononuclear) / Leukocytes (neutrophilic) / Lipopolysaccharides / Lymphocytes / Lymphocytes T / Medicine / Mesenchyme / Neutrophils / Penicillin / Peripheral blood mononuclear cells / Placenta / stem cells / Stromal cells / Stromal Cells - metabolism / Th1 Cells / Tumor necrosis factor