Human Wharton's Jelly-Derived Mesenchymal Stromal Cells Primed by Tumor Necrosis Factor-α and Interferon-γ Modulate the Innate and Adaptive Immune Cells of Type 1 Diabetic Patients

• Published in: Frontiers in immunology Vol. 12; p. 732549
• Main Authors: Mrahleh, Mairvat Al, Matar, Suzan, Jafar, Hanan, Wehaibi, Suha, Aslam, Nazneen, Awidi, Abdalla
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 28.09.2021
• Subjects: Adaptive Immunity; Adolescent; Adult; Cell Communication; Cell Differentiation; Cell Proliferation; Cells, Cultured; Coculture Techniques; Dendritic Cells - immunology; Dendritic Cells - metabolism; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - metabolism; Female; Gene Expression Regulation; Humans; Immunity, Innate; Immunology; Immunomodulation; Interferon-gamma - pharmacology; Lymphocyte Activation; Male; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - immunology; Mesenchymal Stem Cells - metabolism; Pregnancy; priming; regulatory T cells; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; tolerogenic dendritic cells; Tumor Necrosis Factor-alpha - pharmacology; type 1 diabetes; Wharton Jelly - cytology; Wharton’s jelly-derived mesenchymal stromal cells; Young Adult; regulatory T cells; priming; type 1 diabetes; Wharton’s jelly-derived mesenchymal stromal cells; tolerogenic dendritic cells; Immunomodulation
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.732549

The unique immunomodulation and immunosuppressive potential of Wharton's jelly-derived mesenchymal stromal cells (WJ-MSCs) make them a promising therapeutic approach for autoimmune diseases including type 1 diabetes (T1D). The immunomodulatory effect of MSCs is exerted either by cell-cell contact or by secretome secretion. Cell-cell contact is a critical mechanism by which MSCs regulate immune-responses and generate immune regulatory cells such as tolerogenic dendritic cells (tolDCs) and regulatory T cell (Tregs). In this study, we primed WJ-MSCs with TNF-α and IFN-γ and investigated the immunomodulatory properties of primed WJ-MSCs on mature dendritic cells (mDCs) and activated T cells differentiated from mononuclear cells (MNCs) of T1D patient's. Our findings revealed that primed WJ-MSCs impaired the antigen-mediated immunity, upregulated immune-tolerance genes and downregulated immune-response genes. We also found an increase in the production of anti-inflammatory cytokines and suppression of the production of pro-inflammatory cytokines. Significant upregulation of and augmented an immunosuppressive effect on adaptive T cell immunity which represented a strong evidence in support of the formation of Tregs. Furthermore, upregulation of many critical genes involved in the immune-tolerance mechanism ( and was detected. Interestingly, upregulation of genes express a strong evidence to switch immunostimulatory response toward immunoregulatory response. We conclude that WJ-MSCs primed by TNF-α and IFN-γ may represent a promising tool to treat the autoimmune disorders and can provide a new evidence to consider MSCs- based therapeutic approach for the treatment of TID.