Immunology: Blocking Interleukin-22 can alleviate stress-induced anemias in mice

Interleukin-22 (IL-22), an immune signaling molecule, can inhibit red blood cell production and thus lead to anemia in mice, according to a paper published in Nature Immunology. These findings may have implications for treating stress-induced anemias in people.

Environmental exposure to radiation, pesticides or heavy metals such as lead or mercury can increase the risk of developing myelodysplastic syndromes (MDS)—a group of cancers characterized by the failure of blood cells in the bone marrow to mature—which is commonly accompanied by severe anemia. However, the mechanisms driving this particular symptom are not fully understood.

Laurie Glimcher and colleagues identified a stress-induced signature that led to decreased red blood cell production in mice with impaired expression of Riok2—a gene whose human equivalent is encoded on a region of chromosome 5 that is deleted in 10–15% of patients with MDS. The authors found that reduced Riok2 expression led to increased expression of the immune signaling molecule IL-22. They observed that young red blood cells in the mouse model were especially sensitive to IL-22 and that increased levels of the molecule blocked the red blood cells’ maturation, which led to cell death. The authors then demonstrated that neutralizing IL-22 with antibody therapy revived red blood cell production.

The authors also found elevated IL-22 concentrations in a cohort of human patients with MDS with the chromosome 5 mutation, as well as in a separate cohort of human patients with anemia and chronic kidney disease, suggesting that the signaling molecule may represent a biomarker for these conditions.

The authors conclude that, although further research is needed, taken together, these findings indicate that targeting the IL-22 signaling pathway may help alleviate stress-induced anemias in human patients.