Mesenchymal PGD₂ activates an ILC2-Treg axis to promote proliferation of normal and malignant HSPCs.

ABSTRACT: Cyclooxygenase (COX)-dependent production of prostaglandins (PGs) is known to play important roles in tumorigenesis. PGD₂ has recently emerged as a key regulator of tumor- and inflammation-associated functions. Here we show that mesenchymal stromal cells (MSCs) from patients with acute myeloid leukemia (AML) or normal MSCs overexpressing COX2 promote proliferation of co-cultured hematopoietic stem and progenitor cells (HSPCs), which can be prevented by treatment with COX2 knockdown or TM30089, a specific antagonist of the PGD₂ receptor CRTH2. Mechanistically, we demonstrate that PGD₂-CRTH2 signaling acts directly on type 2 innate lymphoid cells (ILC2s), potentiating their expansion and driving them to produce Interleukin-5 (IL-5) and IL-13. Furthermore, IL-

SUBMITTER: Wu L 

PROVIDER: S-EPMC7606225 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature