An inflammatory loop between spleen-derived myeloid cells and CD4+ T cells leads to accumulation of long-lived plasma cells that exacerbates lupus autoimmunity
- Title
- An inflammatory loop between spleen-derived myeloid cells and CD4+ T cells leads to accumulation of long-lived plasma cells that exacerbates lupus autoimmunity
- Author
- 남진우
- Keywords
- long-lived plasma cell; myeloid-derived suppressor cell; autoantibody; lupus; sanroque mice
- Issue Date
- 2021-02
- Publisher
- FRONTIERS MEDIA SA
- Citation
- FRONTIERS IN IMMUNOLOGY, v. 12, article no. 631472, Page. 1-19
- 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 extramedullarymyelopoiesis under
the proinflammatory cytokine milieu during lupus progression. SDMCs promoted the
development of IFN-g-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.
- URI
- https://www.frontiersin.org/articles/10.3389/fimmu.2021.631472/fullhttps://repository.hanyang.ac.kr/handle/20.500.11754/175623
- ISSN
- 1664-3224
- DOI
- 10.3389/fimmu.2021.631472
- Appears in Collections:
- COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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