RT Journal Article
SR Electronic
T1 Osteoclasts contribute to early development of chronic inflammation by promoting dysregulated hematopoiesis and myeloid skewing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.09.418137
DO 10.1101/2020.12.09.418137
A1 Maria-Bernadette Madel
A1 Lidia Ibáñez
A1 Thomas Ciucci
A1 Julia Halper
A1 Majlinda Topi
A1 Henri-Jean Garchon
A1 Matthieu Rouleau
A1 Christopher G Mueller
A1 Laurent Peyrin-Biroulet
A1 David Moulin
A1 Claudine Blin-Wakkach
A1 Abdelilah Wakkach
YR 2020
UL http://biorxiv.org/content/early/2020/12/11/2020.12.09.418137.abstract
AB Increased myelopoiesis is a hallmark of many chronic inflammatory diseases. However, the mechanisms involved in the myeloid skewing of hematopoiesis upon inflammation are still incompletely understood. Here, we identify an unexpected role of bone-resorbing osteoclasts in promoting hematopoietic stem cell (HSC) proliferation and differentiation towards myeloipoiesis in the early phases of chronic colitis. RNAseq analysis revealed that osteoclasts in colitis differ from control ones and overexpress genes involved in the remodeling of HSC niches. We showed that colitic osteoclasts modulate the interaction of HSCs with their niche and promote myeloid differentiation. Increased osteoclast activity was correlated with an augmentation of myelopoiesis in patients with chronic colitis. Therapeutic blockade of osteoclasts reduced HSC proliferation and myeloid skewing and resulted in a decreased inflammation and severity of colitis. Together, these data identify osteoclasts as potent regulators of HSCs and promising target in chronic colitis.Competing Interest StatementThe authors have declared no competing interest.