Masato Kubo

Publications (2)35.21 Total impact

• Source

  Available from: Batu Erman

  Article: Coreceptor gene imprinting governs thymocyte lineage fate.

  Stanley Adoro, Thomas McCaughtry, Batu Erman, Amala Alag, François Van Laethem, Jung-Hyun Park, Xuguang Tai, Motoko Kimura, Lie Wang, Alex Grinberg, Masato Kubo, Remy Bosselut, Paul Love, Alfred Singer
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  ABSTRACT: Immature thymocytes are bipotential cells that are signalled during positive selection to become either helper- or cytotoxic-lineage T cells. By tracking expression of lineage determining transcription factors during positive selection, we now report that the Cd8 coreceptor gene locus co-opts any coreceptor protein encoded within it to induce thymocytes to express the cytotoxic-lineage factor Runx3 and to adopt the cytotoxic-lineage fate, findings we refer to as 'coreceptor gene imprinting'. Specifically, encoding CD4 proteins in the endogenous Cd8 gene locus caused major histocompatibility complex class II-specific thymocytes to express Runx3 during positive selection and to differentiate into CD4(+) cytotoxic-lineage T cells. Our findings further indicate that coreceptor gene imprinting derives from the dynamic regulation of specific cis Cd8 gene enhancer elements by positive selection signals in the thymus. Thus, for coreceptor-dependent thymocytes, lineage fate is determined by Cd4 and Cd8 coreceptor gene loci and not by the specificity of T-cell antigen receptor/coreceptor signalling. This study identifies coreceptor gene imprinting as a critical determinant of lineage fate determination in the thymus.
  The EMBO Journal 01/2012; 31(2):366-77. · 9.20 Impact Factor
• Article: Signaling by intrathymic cytokines, not T cell antigen receptors, specifies CD8 lineage choice and promotes the differentiation of cytotoxic-lineage T cells.

  Jung-Hyun Park, Stanley Adoro, Terry Guinter, Batu Erman, Amala S Alag, Marta Catalfamo, Motoko Y Kimura, Yongzhi Cui, Philip J Lucas, Ronald E Gress, Masato Kubo, Lothar Hennighausen, Lionel Feigenbaum, Alfred Singer
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  ABSTRACT: Immature CD4(+)CD8(+) (double-positive (DP)) thymocytes are signaled via T cell antigen receptors (TCRs) to undergo positive selection and become responsive to intrathymic cytokines such as interleukin 7 (IL-7). We report here that cytokine signaling is required for positively selected thymocytes to express the transcription factor Runx3, specify CD8 lineage choice and differentiate into cytotoxic-lineage T cells. In DP thymocytes genetically engineered to be cytokine responsive, IL-7 signaling induced TCR-unsignaled DP thymocytes to express Runx3 and to differentiate into mature CD8(+) T cells, completely circumventing positive selection. We conclude that TCR-mediated positive selection converts DP cells into cytokine-responsive thymocytes, but it is subsequent signaling by intrathymic cytokines that specifies CD8 lineage choice and promotes differentiation into cytotoxic-lineage T cells.
  Nature Immunology 03/2010; 11(3):257-64. · 26.01 Impact Factor