Delayed type hypersensitivity-induced myeloid-derived suppressor cells regulate autoreactive T cells

• Verfasst von: Singh, Vibhuti [VerfasserIn]
• Verfasst von: Mueller, Ulrike [VerfasserIn]
• Verfasst von: Freyschmidt-Paul, Pia [VerfasserIn]
• Verfasst von: Zöller, Margot [VerfasserIn]
• Titel: Delayed type hypersensitivity-induced myeloid-derived suppressor cells regulate autoreactive T cells
• Verf.angabe: Vibhuti Singh, Ulrike Mueller, Pia Freyschmidt-Paul and Margot Zöller
• E-Jahr: 2011
• Jahr: 04 July 2011
• Umfang: 12 S.
• Fussnoten: Gesehen am 14.10.2022
• Titel Quelle: Enthalten in: European journal of immunology
• Ort Quelle: Weinheim : Wiley-VCH, 1971
• Jahr Quelle: 2011
• Band/Heft Quelle: 41(2011), 10, Seite 2871-2882
• ISSN Quelle: 1521-4141
• DOI: doi:10.1002/eji.201141696
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Apoptosis
• Sach-SW: Autoimmunity
• Sach-SW: Delayed type hypersensitivity
• Sach-SW: Myeloid-derived suppressor cells
• Sach-SW: Signal transduction
• K10plus-PPN: 181896449X

Abstract

Mild but efficient treatments of autoimmune diseases are urgently required. One such therapy, long-term maintenance of chronic delayed type hypersensitivity, has been described for alopecia areata (AA), a hair follicle-affecting autoimmune disease. The molecular mechanisms underlying the therapeutic efficacy are unknown, but may involve myeloid-derived suppressor cells (MDSCs). AA-affected mice were treated with squaric acid dibutyl ester (SADBE). The immunoreactivity of SADBE-treated AA lymphocytes and of AA lymphocytes co-cultured with SADBE-induced MDSCs was analyzed. The curative effect of SADBE was abolished by all-transretinoic acid, which drives MDSCs into differentiation, confirming a central role for MDSCs in therapeutic SADBE treatment. SADBE and SADBE-induced MDSCs strongly interfered with sustained autoreactive T-cell proliferation in response to AA skin lysate (autoantigen), which was accompanied by weak ζ-chain down-regulation and strongly impaired Lck activation. In contrast, activation of the mitochondrial apoptosis pathway and blockade of the anti-apoptotic PI3K/Akt pathway by SADBE-induced MDSCs did not require T-cell receptor engagement. Apoptosis induction correlated with high TNF-α expression in SADBE-induced MDSCs and elevated TNFRI levels in AA lymphocytes. SADBE-induced MDSCs interfere with persisting autoreactive T-cell proliferation and promote apoptosis of these T cells, which qualifies MDSCs induced and maintained by chronic delayed type hypersensitivity reactions as promising therapeutics in organ-related autoimmune diseases.