Research press release


Nature Immunology

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

免疫シグナル伝達分子のインターロイキン22(IL-22)は、赤血球の産生を阻害し、それによってマウスに貧血を引き起こす可能性があることを報告する論文が、Nature Immunology に掲載される。この知見は、ヒトのストレス誘発性貧血を治療する手掛かりとなるかもしれない。


今回、Laurie Glimcherたちの研究チームは、Riok2遺伝子の発現が低下しているマウスにおいて、赤血球の産生減少につながるストレス誘発性のシグネチャーを明らかにした。Riok2遺伝子のヒト相同遺伝子は5番染色体のある領域にコードされており、MDS患者の10~15%でこの領域が欠失している。Glimcherたちは、Riok2の発現を抑制すると、免疫シグナル伝達分子であるIL-22の発現が亢進することを見いだした。マウスモデルでは、若い赤血球が特にIL-22への感受性が高いことが観察され、IL-22レベルが上昇すると赤血球の成熟が妨げられて、これが赤血球の細胞死につながることが分かった。続いてGlimcherたちは、抗体療法によってIL-22を中和すると、赤血球の産生が回復することを示した。



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.

doi: 10.1038/s41590-021-00895-4


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