Role of IRF-4 in adult T cell Leukemia/lymphoma

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1.Optimal binding motif of IRF-4 is identified, by selection and amplification binding(SAAB) method. IRF-4 prefers to the motif, 5'-GAAA-3' flanked by CpG. Similar motifs are found in the promoter of human TRAIL and DCIR.2.By analyzing IRF-4 deficient dendritic cells, we show that IRF-4 is important for CD11b^<high>CD8α conventional DCs. IRF-4 and IRF-8 were expressed in the majority of CD11b^<high>CD4^+CD8α^-DCs and CD CD11b^<low>CD8α^+ DCs, respectively, in a mutually exclusive manner. These results imply that IRF-4 and IRF-8 selectively play critical roles in the development of the DC subsets that express them.3.We investigated the transcriptional control of IRF-4 in B lymphocytes. The IRF-4 promoter analysis reveals that the region between -51 and -28 was required for the basal promoter activity. UV photocrosslinking assays identified a novel 60 kDa protein with a similar sequence preference.4.To clarify the direct involvement of IRF-4 in ATL proliferation, we have applied IRF-4 specific siRNA, however, at present, every attempt to reduce the expression of IRF-4 was found unsuccessful.5.By applying membrane array, we found EBI-1/CCR7 may be one of the target genes of IRF-4. It is consistent with our previous finding that ATLL cells express EBI-1/CCR7 and IRF-4 concomitantly.