MiR ‐15a/16‐1 deficiency induces IL‐10‐producing CD19+ TIM‐1+ cells in tumor microenvironment

AbstractIL ‐10‐producing B cells (B10) are associated with autoimmune diseases, infection and tumours. MiR‐15a/16 as a tumour‐suppressive gene is down‐regulated in several tumours, such as chronic lymphocytic leukaemia, pituitary adenomas and prostate carcinoma. Here, increased frequency of IL‐10‐ producing CD19+ Tim ‐1+ cells was seen in both aged miR ‐15a/16−/− mice (15 ‐18 months) with the onset of B cell leukaemia and young knockout mice (8‐12 weeks) transplanted with hepatic cancer cells. CD19+ Tim ‐1+ cells down ‐regulated the function of effector CD4+CD25low T cells ex vivo dependent on IL ‐10 production, and adoptive transfer of CD19+ Tim ‐1+ cells promoted tumour growth in mice. IL ‐10 production by CD19+ Tim ‐1+ cells was involved with the STAT3 activation. Bioinformatics analysis shows that miR ‐16 targets the 3′‐untranslating region (3′‐UTR) of STAT3 mRNA. Overexpression of miR‐16 in CD19+ Tim ‐1+ cells inhibited STAT3 transcription and its protein expression. Thus, the loss of miR ‐15a/16 promoted induction of regulatory CD19+ Tim ‐1+ cells in tumour microenvironment. These results confirmed that miR ‐15a/16 could be used in tumour therapy due to its inhibition of tumour and regulatory B cells.
Source: Journal of Cellular and Molecular Medicine - Category: Molecular Biology Authors: Tags: ORIGINAL ARTICLE Source Type: research