Blockade of IL-22 signaling reverses erythroid dysfunction in stress-induced anemias
Name
nihms-1670115.pdf
Description
Accepted version
Size
3.4 MB
Format
Adobe PDF
Checksum (MD5)
961a5dfbce2ca6ff0bb5b41eb4068bfc
Author(s)
Raundhal, Mahesh
Ghosh, Shrestha
Myers, Samuel A
Cuoco, Michael S
Singer, Meromit
Carr, Steven A
Waikar, Sushrut S
Bonventre, Joseph V
Ritz, Jerome
Stone, Richard M
Date Issued
March 2021
Journal
Nature Immunology
Publisher
Springer Science and Business Media LLC
Citation
Raundhal, M., Ghosh, S., Myers, S.A. et al. Blockade of IL-22 signaling reverses erythroid dysfunction in stress-induced anemias. Nat Immunol 22, 520–529 (2021).
Version
Author's final manuscript
Abstract
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 (Riok2f/+Vav1cre) led to reduced erythroid precursor frequency leading to anemia. Proteomic analysis of Riok2f/+Vav1cre erythroid precursors suggested immune system activation, and transcriptomic analysis revealed an increase in p53-dependent interleukin (IL)-22 in Riok2f/+Vav1cre 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 Riok2f/+Vav1cre 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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1038/S41590-021-00895-4
