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Wakao, H.

Publications and source records attributed to Wakao, H..

2 recordsLinked to original sources

Mice generated with induced pluripotent stem cells derived from mucosal-associated invariant T cells

The function of mucosal-associated invariant T (MAIT) cells, a burgeoning member of innate-like T cells abundant in humans and implicated in many diseases, remains obscure. To explore this, mice with a rearranged T cell receptor (TCR) or {beta} locus, specific for MAIT cells, were generated via induced pluripotent stem cells derived from MAIT cells and designated V19 and V{beta}8 mice, respectively. Both mice expressed large amounts of MAIT cells. The MAIT cells from these mice were activated by cytokines and an agonist to produce IFN-{gamma} and IL-17. While V{beta}8 mice showed resistance in a cancer metastasis model, V19 mice did not. Adoptive transfer of MAIT cells from the latter into the control mice, however, recapitulated the resistance. This has implications for understanding the role of MAIT cells in health and disease and in developing treatments for the plethora of diseases in which MAIT cells are implicated.

immunology↗

Reprogramming and redifferentiation of mucosal-associated invariant T cells reveals tumor inhibitory activity

Mucosal-associated invariant T (MAIT) cells belong to a family of innate-like T cells that bridge innate and adaptive immunities. Although MAIT cells have been implicated in tumor immunity, it currently remains unclear whether they function as tumor promoting or inhibitory cells. Therefore, we herein used induced pluripotent cell (iPSC) technology to investigate this issue. Murine MAIT cells were reprogrammed into iPSCs and redifferentiated towards MAIT-like cells (m-reMAIT cells). m-reMAIT cells were activated by an agonist and MR1-tetramer, a reagent to detect MAIT cells, in the presence and absence of antigen-presenting cells. This activation accompanied protein tyrosine phosphorylation and the production of T helper (Th)1-, Th2-, and Th17-cytokines and inflammatory chemokines. Upon adoptive transfer, m-reMAIT cells migrated to different organs with maturation in mice. Furthermore, m-reMAIT cells prolonged mouse survival upon tumor inoculation through the NK cell-mediated reinforcement of cytolytic activity. Collectively, the present results demonstrated the utility and role of m-reMAIT cells in tumor immunity, and will contribute to insights into the function of MAIT cells in immunity.

cancer biology↗