Deficient regulatory innate lymphoid cells and differential expression of miRNAs in patients with haematological diseases

Background: A new regulatory subpopulation of ILCs, ILCregs, has been identified in mouse and human intestines. ILCregs constitutively express id2, id3, sox4, tgfbr1, tgfbr2, il2rb and il2rg genes and share characteristics with both innate lymphoid cells and regulatory cells. However, the significance of ILCregs and its associated miRNAs in patients with haematological diseases, such as AML, MDS, AA, has yet to be explored. In this study, we evaluate ILCregs frequency, associated miRNA quantification, and their significance in patients with AML, MDS, AA and normal donors (ND). Methods: Using four color combinations of surface and intracellular antibody staining CD45+Lin-CD127+IL-10+ ILCregs from 30 ND patients, 42 diagnosed with AML, 30 with MDS, and 30 with AA were measured by flow cytometry. miRNAs quantification from plasma and bone marrow cells were measured by NGS. Results: Our results showed that the frequencies of ILCregs in AML, MDS, and AA patients were significantly lower than that in ND (p <0.01). Variable frequency differences of ILCregs among these four groups were also observed. miRNA detection results showed a variety of miRNA expression patterns in ND and these different patient groups. Analysis of miRNAs from ILCregs associated genes, including id2, id3, sox4, tgfbr1, tgfbr2, il2rb, and il3rg, from ND, AML, MDS, and AA demonstrated significant difference between ND and these three different patient groups. The relationship between ILCregs and its associated miRNAs was explored between ND and AML, MDS, and AA patients. Conclusion: Our study enumerated ILCregs and measured miRNAs in AML, MDS and AA patient samples at the first time. The results demonstrated deficiency of ILCreg and miRNA differential expression in patients with AML, MDS, and AA.

Author(s): Jifeng Yu, Li Y, Sun L, Han L, Pan Y, Liu Y, Zhang D, Xing H, Xie X, Wan D, Jiang Z

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