An Inflammatory Loop Between Spleen-Derived Myeloid Cells and CD4+ T Cells Leads to Accumulation of Long-Lived Plasma Cells That Exacerbates Lupus Autoimmunity

Abstract

Splenic long-lived plasma cells are abnormally numerous and deleterious in systemic autoimmune diseases, yet how they accumulate remains poorly understood. We demonstrate here that a pathological role of spleen-derived CD11b+Gr-1+ myeloid cells (SDMCs) underpins the accumulation of splenic long-lived plasma cells in a lupus-prone model named sanroque. We found that SDMCs were progressively accumulated in sanroque mice from the early clinical phase. Transcriptome profiles revealed that SDMCs have a predominant shift toward an inflammatory phenotype relative to the bone marrow-derived counterparts and are distinct from neutrophils and monocytes. SDMCs were expanded in situ via splenic extramedullary myelopoiesis under the proinflammatory cytokine milieu during lupus progression. SDMCs promoted the development of IFN-γ-secreting Th1 and follicular helper T cells, thereby licensing CD4+ T cells to be pathologic activators of SDMCs and plasma cells. SDMCs also directly promoted the survival of plasma cells by providing B-cell activating factor of the TNF family. The frequency of SDMCs correlated with that of splenic long-lived plasma cells. Selective depletion of CD11b+Gr-1+ cells reduced autoantibody production in sanroque mice. Thus, our findings suggest that SDMCs expanded in situ establish a positive feedback loop with CD4+ T cells, leading to accumulation of long-lived plasma cells which exacerbates lupus autoimmunity.

Polymorphonuclear myeloid-derived suppressor cells play a proinflammatory role via TNF-α + B cells through BAFF/BTK/NF-B signaling pathway in the pathogenesis of collagen-induced arthritis mice

“…Therefore, it would be interesting to verify whether PMN-MDSCs can modulate B cell activity in autoimmune arthritis. Crook et al (26) found that M-MDSCs from spleens of CIA mice, but not Ly6G + cells from the BM, inhibited B cell proliferation and antibody production, while Jang et al (27) found that spleens derived from CD11b + Gr-1 + cells directly promoted the survival of plasma cells in a lupus-prone mouse model, and found that CD11b + Ly6G + PMN-MDSCs from spleens of CIA could support B cells in vivo and in vitro . To our knowledge, it is the first demonstration that PMN-MDSCs from CIA mice not only support the B cells' survival, but also promote TNF-?…”

Polymorphonuclear myeloid‐derived suppressor cells play a proinflammatory role via TNF‐α+ B cells through BAFF/BTK/NF‐κB signalling pathway in the pathogenesis of collagen‐induced arthritis mice

“…Therefore, it would be interesting to verify whether PMN‐MDSCs could modulate B cells activities in autoimmune arthritis. Crook et al [26] found that M‐MDSCs from spleen of CIA mouse, not Ly6G + cells from BM, inhibited B cells proliferation and antibody production, while Jang et al [27] found that spleen‐derived CD11b + Gr‐1 + cells directly promoted the survival of plasma cells in Lupus‐prone mouse model, we also found that CD11b + Ly6G + PMN‐MDSCs from spleen of CIA could support B cells in vivo and in vitro. To our knowledge, it is the first demonstration that PMN‐MDSCs from CIA mice not only support B cells' survival, but also promote TNF‐α secretion via BAFF, which was probably a potential pathogenesis of RA.…”

Pharmacological Evaluation of Different Extracts of Asparagus officinalis (Asparagaceae) as an Analgesic, Anti-Inflammatory and Anti-arthritic Agent in Rats

“…The research has shown that spleen-derived CD11b+Gr-1+ myeloid cells (SDMCs) play a pathogenic role in the deposition of splenic long-lived plasma cells in the sanroque lupus-prone mouse and that SDMCs can be accumulate. [33] Form qualitative phytochemical assays it is clear that Asparagus officinalis is reach in terpenoids and flavonoids. Various routes of action are already proven for mode of action against inflammation and arthritis by both flavonoids and terpenoids.…”