Related Experiment Video
Updated: Jan 10, 2026
Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
Myeloid-Derived Suppressor Cell-Derived Interferon-β Promotes T Follicular Helper Cell Response and Exacerbates Lupus
Ke Rui1, Zixiang Chen1,2, Jun Liu1,2
1Department of Laboratory Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Objective:
Increasing evidence highlights a critical role of T follicular helper (Tfh) cells in autoimmune pathogenesis. This study aimed to identify inflammatory cytokines involved in driving Tfh cell responses in systemic lupus erythematosus (SLE).
Methods:
The circulating Tfh frequencies and interferon (IFN)-β levels were analyzed for correlations with disease activities in patients with SLE. Both lupus mice with IFN-β treatment and Ifnar1-/- mice with lupus induction were assessed for Tfh cell responses and disease progression. Sorting-purified naive CD4+T cells from Ifnar1-/- mice were adoptively transferred to lupus mice for monitoring Tfh cell differentiation in vivo. In culture, mouse CD4+T cells treated with IFN-β were examined for Tfh cell differentiation and intracellular signaling pathway. The underlying mechanism for IFN-β secretion by myeloid-derived suppressor cells (MDSCs) was investigated by co-immunoprecipitation and Western blotting.
Results:
We found that increased Tfh cells with IFN-I-inducible gene signatures correlated with disease activities in patients with SLE. Consistently, IFN-β treatment markedly enhanced Tfh cell response and exacerbated disease progression in lupus mice. Moreover, mice with IFNAR1 deficiency exhibited attenuated lupus progression with significantly decreased Tfh response. Mechanistically, IFN-β activated the indoleamine 2,3-dioxygenase/kynurenine/aryl hydrocarbon receptor (IDO/Kyn/AhR) axis to promote Tfh cell differentiation. Notably, expanded MDSCs in lupus were found to produce high levels of IFN-β. Further studies showed that the autoantigen activated lymphocyte-derived DNA stimulated IFN-β production by MDSCs via the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING)-dependent pathway.
Conclusion:
These results have demonstrated a novel function of IFN-β in promoting Tfh cell response during lupus progression, which may facilitate the identification of new therapeutic targets for the treatment of SLE.
