Decitabine may effectively treat CMML/MDS-associated inflammatory bowel disease by regulating the Th17/Treg balance

Author:

Luo Guobiao1,Gao Guanlun2,Liu Zengyan3,Wei Ting2,Li Qing-Shan2

Affiliation:

1. Department of Gastroenterology, Guangzhou Red Cross Hospital, Jinan University

2. Department of Hematology, Guangzhou Red Cross Hospital, Jinan University

3. Department of Hematology, Guangzhou First People′s Hospital, Guangzhou Medical University

Abstract

Abstract Background. T helper 17 (Th17) and regulatory T (Treg) cell imbalance in the immune microenvironment is involved in the pathogenesis of myelodysplastic syndrome (MDS) and inflammatory bowel disease (IBD). DNA demethylation agents are the main treatment for MDS/ chronic myelomonocytic leukemia (CMML). However, the clinical efficacy of the demethylation agent decitabine (DAC) in the treatment of MDS /CMML-associated IBD has not been reported. Methods. In this study, Decitabine was used to treat two patients with MDS/CMML-associated inflammatory bowel disease. Clinical efficacy was assessed after 5 courses of DAC treatment. Meanwhile, we performed dynamic monitoring of immune-related indicators in the intestinal, bone marrow, and peripheral blood microenvironment of one patient with CMML-associated ulcerative colitis. Results. IBD was improved in 2 patients with haematological remission in MDS or CMML. Immunohistochemical analysis of bone marrow specimens showed that PD-1, PD-L1, and Foxp3 were upregulated, and IL-17 was downregulated. In the bone marrow and intestine, quantitative RT-PCR showed that the mRNA level of IL-17 decreased after DAC treatment, whereas those Foxp3, PD-1, and PD-L1 mRNA increased. Flow cytometry showed that the percentage of Th17 cells in peripheral blood mononuclear cells decreased, whereas that of Treg cells increased. Conclusions. Our results suggest that DAC may effectively treat CMML/MDS associated IBD by affecting the balance of Th17/Treg via PD-1/PD-L1 pathway in the immune microenvironment.

Publisher

Research Square Platform LLC

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