Inhibition of inositol kinase B controls acute and chronic graft-versus-host disease
Journal article published in 2020 by
Govindarajan Thangavelu,
Jing Du,
Katelyn G. Paz,
Michael Loschi 
,
Michael C. Zaiken ,
Ryan Flynn,
Patricia A. Taylor,
Andrew Kemal Kirchmeier ,
Angela Panoskaltsis-Mortari,
Leo Luznik,
Kelli P. MacDonald ,
Geoffrey R. Hill ,
Ivan Maillard,
David H. Munn,
Jonathan S. Serody
and other authors.
,
Michael C. Zaiken ,
Ryan Flynn,
Patricia A. Taylor,
Andrew Kemal Kirchmeier ,
Angela Panoskaltsis-Mortari,
Leo Luznik,
Kelli P. MacDonald ,
Geoffrey R. Hill ,
Ivan Maillard,
David H. Munn,
Jonathan S. Serody
and other authors.
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Abstract
T-cell activation leads to regulated increases in cytoplasmic calcium through inositol 1,4,5-triphosphate (IP3), a process balanced by phosphorylation and inactivation of IP3 by inositol 1,4,5-trisphosphate 3-kinase B (Itpkb). The investigators demonstrate that inhibition of Itpkb sustains increased intracellular Ca, leads to T-cell apoptosis, and inhibits graft-versus-host disease without impairing graft-versus-leukemia effects.