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

Eunkyeong Jang, Somi Cho, Sungjin Pyo, Jin Wu Nam, Jeehee Youn

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number631472
JournalFrontiers in immunology
Volume12
DOIs
StatePublished - 2021 Feb 11
Externally publishedYes

Keywords

  • autoantibody
  • long-lived plasma cell
  • lupus
  • myeloid-derived suppressor cell
  • sanroque mice

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