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Nat Immunol DOI:10.1038/s41590-021-00895-4

Blockade of IL-22 signaling reverses erythroid dysfunction in stress-induced anemias.

Publication TypeJournal Article
Year of Publication2021
AuthorsRaundhal, M, Ghosh, S, Myers, SA, Cuoco, MS, Singer, M, Carr, SA, Waikar, SS, Bonventre, JV, Ritz, J, Stone, RM, Steensma, DP, Regev, A, Glimcher, LH
JournalNat Immunol
Volume22
Issue4
Pages520-529
Date Published2021 Apr
ISSN1529-2916
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 (Riok2Vav1) led to reduced erythroid precursor frequency leading to anemia. Proteomic analysis of Riok2Vav1 erythroid precursors suggested immune system activation, and transcriptomic analysis revealed an increase in p53-dependent interleukin (IL)-22 in Riok2Vav1 CD4 T cells (T22). 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 Riok2Vav1 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.

DOI10.1038/s41590-021-00895-4
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/33753942?dopt=Abstract

Alternate JournalNat Immunol
PubMed ID33753942
PubMed Central IDPMC8026551
Grant ListU24-CA210986 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
2P01CA066996 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
P50 CA206963 / CA / NCI NIH HHS / United States
U24 CA210986 / CA / NCI NIH HHS / United States
P01 CA066996 / CA / NCI NIH HHS / United States
1P50CA206963 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
U01 CA214125 / CA / NCI NIH HHS / United States
U01 CA214125 / CA / NCI NIH HHS / United States