TY - JOUR
T1 - Blimp-1 induces and Hobit maintains the cytotoxic mediator granzyme B in CD8 T cells
AU - Kragten, Natasja A. M.
AU - Behr, Felix M.
AU - Vieira Braga, Felipe A.
AU - Remmerswaal, Ester B. M.
AU - Wesselink, Thomas H.
AU - Oja, Anna E.
AU - Hombrink, Pleun
AU - Kallies, Axel
AU - van Lier, Rene A. W.
AU - Stark, Regina
AU - van Gisbergen, Klaas P. J. M.
PY - 2018
Y1 - 2018
N2 - CD8 T cells acquire cytotoxic molecules including granzyme B during effector differentiation. Both tissue-resident memory CD8 T cells (Trm) and circulating CD45RA+ effector-type T cells (Temra) cells have the ability to retain granzyme B protein expression into the memory phase, but it is unclear how this persistence of cytolytic activity is regulated during steady state. Previously, we have described that the transcriptional regulators Hobit and Blimp-1 have overlapping target genes that include granzyme B, but their impact on the regulation of cytotoxicity in Trm and Temra cells during homeostasis has remained unclear. We examined the expression regulation of Hobit and Blimp-1 in murine and human CD8 T-cells to determine their timeframe of activity. While Blimp-1 mRNA was expressed throughout effector and memory T cells, Blimp-1 protein, was only transiently expressed during the effector stage. In contrast, Hobit mRNA and protein expression was stably maintained during quiescence, but downregulated after activation. Notably, Blimp-1 was required for expression of granzyme B in murine effector T cells and Trm, while Hobit specifically regulated granzyme B in murine Trm during the memory phase. These findings suggest that Blimp-1 initiates cytotoxic effector function and that Hobit maintains cytotoxicity in a deployment-ready modus in Trm.
AB - CD8 T cells acquire cytotoxic molecules including granzyme B during effector differentiation. Both tissue-resident memory CD8 T cells (Trm) and circulating CD45RA+ effector-type T cells (Temra) cells have the ability to retain granzyme B protein expression into the memory phase, but it is unclear how this persistence of cytolytic activity is regulated during steady state. Previously, we have described that the transcriptional regulators Hobit and Blimp-1 have overlapping target genes that include granzyme B, but their impact on the regulation of cytotoxicity in Trm and Temra cells during homeostasis has remained unclear. We examined the expression regulation of Hobit and Blimp-1 in murine and human CD8 T-cells to determine their timeframe of activity. While Blimp-1 mRNA was expressed throughout effector and memory T cells, Blimp-1 protein, was only transiently expressed during the effector stage. In contrast, Hobit mRNA and protein expression was stably maintained during quiescence, but downregulated after activation. Notably, Blimp-1 was required for expression of granzyme B in murine effector T cells and Trm, while Hobit specifically regulated granzyme B in murine Trm during the memory phase. These findings suggest that Blimp-1 initiates cytotoxic effector function and that Hobit maintains cytotoxicity in a deployment-ready modus in Trm.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85052499360&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30051906
U2 - https://doi.org/10.1002/eji.201847771
DO - https://doi.org/10.1002/eji.201847771
M3 - Article
C2 - 30051906
SN - 0014-2980
VL - 48
SP - 1644
EP - 1662
JO - European journal of immunology
JF - European journal of immunology
IS - 10
ER -