| First Author | Raundhal M | Year | 2021 |
| Journal | Nat Immunol | Volume | 22 |
| Issue | 4 | Pages | 520-529 |
| PubMed ID | 33753942 | Mgi Jnum | J:305794 |
| Mgi Id | MGI:6706614 | Doi | 10.1038/s41590-021-00895-4 |
| Citation | Raundhal M, et al. (2021) Blockade of IL-22 signaling reverses erythroid dysfunction in stress-induced anemias. Nat Immunol 22(4):520-529 |
| abstractText | Patients with myelodysplastic syndromes (MDSs) display severe anemia but the mechanisms underlying this phenotype are incompletely understood. Right open-reading-frame kinase 2 (RIOK2) encodes a protein kinase located at 5q15, a region frequently lost in patients with MDS del(5q). Here we show that hematopoietic cell-specific haploinsufficient deletion of Riok2 (Riok2(f/+)Vav1(cre)) led to reduced erythroid precursor frequency leading to anemia. Proteomic analysis of Riok2(f/+)Vav1(cre) erythroid precursors suggested immune system activation, and transcriptomic analysis revealed an increase in p53-dependent interleukin (IL)-22 in Riok2(f/+)Vav1(cre) CD4(+) T cells (TH22). Further, we discovered that the IL-22 receptor, IL-22RA1, was unexpectedly present on erythroid precursors. Blockade of IL-22 signaling alleviated anemia not only in Riok2(f/+)Vav1(cre) mice but also in wild-type mice. Serum concentrations of IL-22 were increased in the subset of patients with del(5q) MDS as well as patients with anemia secondary to chronic kidney disease. This work reveals a possible therapeutic opportunity for reversing many stress-induced anemias by targeting IL-22 signaling. |
