Plasma Cells Are Obligate Effectors of Enhanced Myelopoiesis in Aging Bone Marrow.

Abstract:

:Aging results in increased myelopoiesis, which is linked to the increased incidence of myeloid leukemias and production of myeloid-derived suppressor cells. Here, we examined the contribution of plasma cells (PCs) to age-related increases in myelopoiesis, as PCs exhibit immune regulatory function and sequester in bone marrow (BM). PC number was increased in old BM, and they exhibited high expression of genes encoding inflammatory cytokines and pathogen sensors. Antibody-mediated depletion of PCs from old mice reduced the number of myeloid-biased hematopoietic stem cells and mature myeloid cells to levels in young animals, but lymphopoiesis was not rejuvenated, indicating that redundant mechanisms inhibit that process. PCs also regulated the production of inflammatory factors from BM stromal cells, and disruption of the PC-stromal cell circuitry with inhibitors of the cytokines IL-1 and TNF-α attenuated myelopoiesis in old mice. Thus, the age-related increase in myelopoiesis is driven by an inflammatory network orchestrated by PCs.

journal_name

Immunity

journal_title

Immunity

authors

Pioli PD,Casero D,Montecino-Rodriguez E,Morrison SL,Dorshkind K

doi

10.1016/j.immuni.2019.06.006

subject

Has Abstract

pub_date

2019-08-20 00:00:00

pages

351-366.e6

issue

2

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(19)30276-6

journal_volume

51

pub_type

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