Sustained increase in cytokine levels in SLE may induce defective
expansion of MDSCs
Research has shown that the early depletion of MDSCs in lupus mice can
significantly accelerate SLE during the progression of renal injury and
the formation of auto-reactive plasma cells 94.
Contrarily, the depletion of MDSCs with more advanced disease has been
shown not to affect the progression of lupus 94. It
has been established that the MDSC population would expand in response
to inflammatory stimulation to suppress inflammation83, 95. Compared with that of non-lupus prone mice,
the MDSC populations of lupus mice have been shown to abate when in an
inflammation condition 95. Recent in vivo mouse
studies have demonstrated that defects occur during the expansion of
MDSCs in lupus mice when responding to inflammation compared with the
expansion of MDSCs in non-lupus prone mice 95.
Increased level of cytokines, such as TNF-α, IL-6, and IFN-γ, can build
the inflammatory milieu in SLE 44, 68, 89, 90. MDSCs
have the potential to differentiate into macrophage and dendritic cells
in inflammatory conditions, such as under increased levels of TNF-α,
IL-6, and IFN-γ 89, 90. According these results, we
speculate that MDSCs may play a regulatory role in the immune system in
SLE and that increased level of cytokines (including TNF-α, IL-6, and
IFN-γ) induce the expansion of MDSCs in SLE. Simultaneously sustained
increases in the levels of cytokines, such as TNF-α, IL-6, and IFN-γ,
may also promote more MDSCs to differentiate into macrophage and
dendritic cells. This can break the balance between self-tolerance
(induced by MDSCs) and inflammation (induced by the sustained increase
in cytokines; Figure 4). This imbalance may decrease the expansion of
MDSCs, or result in so-called “proliferation defects” in MDSCs.