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

Vibhuti Singh¹, Ulrike Mueller, Pia Freyschmidt-Paul

¹Department of Tumor Cell Biology, University Hospital of Surgery, Heidelberg, Germany.

European Journal of Immunology

|July 6, 2011

Summary

Myeloid-derived suppressor cells (MDSCs) are key to squaric acid dibutyl ester (SADBE) treatment for alopecia areata. SADBE-induced MDSCs halt T-cell proliferation and promote apoptosis, offering a new therapeutic avenue for autoimmune diseases.

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Development of Stem Cell-derived Antigen-specific Regulatory T Cells Against Autoimmunity

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Published on: November 8, 2016

Area of Science:

Immunology
Dermatology
Cell Biology

Background:

Autoimmune diseases like alopecia areata (AA) require mild yet effective treatments.
The therapeutic mechanisms of chronic delayed type hypersensitivity maintenance therapy for AA are not fully understood.
Myeloid-derived suppressor cells (MDSCs) are hypothesized to play a role in the efficacy of these treatments.

Purpose of the Study:

To investigate the role of MDSCs in the therapeutic effects of squaric acid dibutyl ester (SADBE) for AA.
To elucidate the molecular mechanisms by which SADBE-induced MDSCs modulate autoreactive T-cells in AA.

Main Methods:

Treatment of AA-affected mice with SADBE.
Analysis of lymphocyte immunoreactivity following SADBE treatment and co-culture with SADBE-induced MDSCs.
Assessment of T-cell activation markers (ζ-chain, Lck), apoptosis pathways (mitochondrial, PI3K/Akt), and cytokine expression (TNF-α).

Main Results:

All-transretinoic acid abolished the curative effect of SADBE, confirming a critical role for MDSCs.
SADBE and induced MDSCs significantly inhibited autoreactive T-cell proliferation and Lck activation.
MDSCs induced apoptosis in T-cells independently of T-cell receptor engagement, correlated with high TNF-α and TNFRI levels.

Conclusions:

SADBE-induced MDSCs effectively suppress autoreactive T-cell proliferation and promote their apoptosis.
MDSCs generated through chronic delayed type hypersensitivity reactions are promising therapeutic agents for organ-specific autoimmune diseases.
This study highlights MDSCs as a potential therapeutic target for managing autoimmune conditions like AA.