Adoptive Cell Therapy of Induced Regulatory T Cells Expanded by Tolerogenic Dendritic Cells on Murine Autoimmune Arthritis.

Publisher: Wiley Country of Publication: Egypt NLM ID: 101627166 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2314-7156 (Electronic) Linking ISSN: 23147156 NLM ISO Abbreviation: J Immunol Res Subsets: MEDLINE

Publication: 2024- : [Hoboken, NJ] : Wiley
Original Publication: Cairo, Egypt : Hindawi Publishing Corporation, [2014]-

Immune Tolerance* ; Immunotherapy, Adoptive*; Arthritis, Experimental/*therapy ; Autoimmune Diseases/*therapy ; Dendritic Cells/*immunology ; T-Lymphocytes, Regulatory/*immunology; Animals ; Arthritis, Experimental/immunology ; Autoimmune Diseases/immunology ; Cell Differentiation ; Cell Proliferation ; Cytokines/blood ; Dendritic Cells/drug effects ; Forkhead Transcription Factors/genetics ; Interleukin-17/blood ; Interleukin-6/blood ; Lymphocyte Activation ; Mice ; Mice, Inbred DBA ; T-Lymphocytes, Regulatory/physiology ; Th17 Cells/immunology ; Th17 Cells/physiology ; Transforming Growth Factor beta/metabolism ; Transforming Growth Factor beta/pharmacology ; Tumor Necrosis Factor-alpha/blood

Objective: Tolerogenic dendritic cells (tDCs) can expand TGF- β -induced regulatory T cells (iTregs); however, the therapeutic utility of these expanded iTregs in autoimmune diseases remains unknown. We sought to determine the properties of iTregs expanded by mature tolerogenic dendritic cells (iTreg mtDC ) in vitro and explore their potential to ameliorate collagen-induced arthritis (CIA) in a mouse model.
Methods: After induction by TGF- β and expansion by mature tDCs (mtDCs), the phenotype and proliferation of iTreg mtDC were assessed by flow cytometry. The ability of iTregs and iTreg mtDC to inhibit CD4 ⁺ T cell proliferation and suppress Th17 cell differentiation was compared. Following adoptive transfer of iTregs and iTreg mtDC to mice with CIA, the clinical and histopathologic scores, serum levels of IFN- γ , TNF- α , IL-17, IL-6, IL-10, TGF- β and anti-CII antibodies, and the distribution of the CD4 ⁺ Th subset were assessed.
Results: Compared with iTregs, iTreg mtDC expressed higher levels of Foxp3 and suppressed CD4 ⁺ T cell proliferation and Th17 cell differentiation to a greater extent. In vivo, iTreg mtDC reduced the severity and progression of CIA more significantly than iTregs, which was associated with a modulated inflammatory cytokine profile, reduced anti-CII IgG levels, and polarized Treg/Th17 balance.
Conclusion: This study highlights the potential therapeutic utility of iTreg mtDC in autoimmune arthritis and should facilitate the future design of iTreg immunotherapeutic strategies.

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0 (Cytokines)
0 (Forkhead Transcription Factors)
0 (Foxp3 protein, mouse)
0 (Interleukin-17)
0 (Interleukin-6)
0 (Transforming Growth Factor beta)
0 (Tumor Necrosis Factor-alpha)

Date Created: 20170714 Date Completed: 20180403 Latest Revision: 20181113

20250114

PMC5494067

10.1155/2017/7573154

28702462