IL-1 receptor antagonist prevents bias to myelopoiesis in hematopoietic stem cells and protects from neoplasia

Interleukin-1β (IL-1β) drives hematopoietic stem cell (HSC) differentiation into the myeloid lineage, and enhanced IL-1β signaling plays a key role in hematological malignancies. However, little is known on the role of its endogenous regulatory cytokine, IL-1 receptor antagonist (IL-1rn), on both healthy and malignant hematopoiesis. Here, we show that in vivo genetic deletion of IL-1rn induces HSC differentiation into the myeloid lineage and hampers B cell development. It also causes damage to the Stromal Compartment of the Bone Marrow. Total RNA was isolated from bone marrow HSC subsets of IL-1 receptor antagonist deficient mice (IL-1rn-KO, n=3) and control C57BL/6J (n=3) mice at the age of 20-25 weeks. HSC were FACS sorted and immunophenotypically defined as follows: lin− c-kit+ Sca-1+ (LSK) CD34- Flt3- long term hematopoietic stem cells (LT-HSC), LSK CD34+ Flt3- short term HSC (ST-HSC) and LSK CD34+ Flt3+ multipotent progenitors (MPP). Mesenchymal stromal cells (MSC) from the BM of the same groups of mice was also used for RNA-Seq. MSC were immunophenitypicall defined as CD45- Ter119- CD31- CD63+ (n=3 per group). RNA was amplified and prepared for RNA-Seq using the SMART-Seq v4 Ultra Low Input RNA kit (Clontech).