Editors' ChoiceStem Cells

Inflammation induces stem cell quiescence

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Science Signaling  29 Oct 2019:
Vol. 12, Issue 605, eaaz9665
DOI: 10.1126/scisignal.aaz9665

Chronic inflammation causes olfactory stem cells to become quiescent and secrete immunomodulatory cytokines.

Olfactory sensory neurons (OSNs) are naturally short-lived but also highly susceptible to damage because they are directly exposed to environmental insults. OSNs are replaced throughout adult life by stem cells in the olfactory epithelium, with different stem cell populations contributing to homeostatic and damage-induced replenishment. Chronic inflammation and aging impair this regenerative capacity. Chen et al. investigated the mechanisms underlying OSN loss in a mouse genetic model of inducible olfactory inflammation that recapitulated the progression of inflammation and OSN loss observed in patients with chronic rhinosinusitis. Inflammation initially stimulated horizontal basal stem cells (HBCs) to proliferate and give rise to new OSNs, but chronic inflammation inhibited OSN generation. Upon removal of the inflammation inducer, HBCs resumed differentiating into OSNs, indicating that they had not lost their regenerative capacity. Prolonged activation of inflammatory nuclear factor κB (NF-κB) signaling in HBCs in vivo stimulated the expression of genes encoding transcription factors that inhibit OSN differentiation and promoted the expression of genes associated with stemness. Prolonged NF-κB signaling also caused HBCs to produce cytokines that recruited and stimulated the proliferation of T cells and macrophages. Similar increases in immune cell infiltration and decreases in HBC proliferation and OSN differentiation were also observed in olfactory tissues from chronic rhinosinusitis patients. Thus, chronic inflammation stimulates HBCs to produce cytokines that recruit immune cells at the expense of neurogenesis. Because immune cell infiltration has also been implicated in the loss of neurogenic capacity in the adult brain (see commentary by Rustenhoven and Kipnis), these findings may also be relevant to inflammatory processes that contribute to impaired neurogenesis in the brain during aging and in disease.

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