Complex Interplay Between MAZR and Runx3 Regulates the Generation of Cytotoxic T Lymphocyte and Memory T Cells
Rica Ramona; Gulich Alexandra F; Tizian Caroline; Hainberger Daniela; Bergthaler Andreas; Viczenczova Csilla; Ellmeier Wilfried; Laiho Asta; Khamina Kseniya; Faux Thomas; Bock Christoph; Sakaguchi Shinya; Elo Laura L; Penz Thomas; Bosselut Remy
Complex Interplay Between MAZR and Runx3 Regulates the Generation of Cytotoxic T Lymphocyte and Memory T Cells
Rica Ramona
Gulich Alexandra F
Tizian Caroline
Hainberger Daniela
Bergthaler Andreas
Viczenczova Csilla
Ellmeier Wilfried
Laiho Asta
Khamina Kseniya
Faux Thomas
Bock Christoph
Sakaguchi Shinya
Elo Laura L
Penz Thomas
Bosselut Remy
FRONTIERS MEDIA SA
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021093048664
https://urn.fi/URN:NBN:fi-fe2021093048664
Tiivistelmä
The BTB zinc finger transcription factor MAZR (also known as PATZ1) controls, partially in synergy with the transcription factor Runx3, the development of CD8 lineage T cells. Here we explored the role of MAZR as well as combined activities of MAZR/Runx3 during cytotoxic T lymphocyte (CTL) and memory CD8(+) T cell differentiation. In contrast to the essential role of Runx3 for CTL effector function, the deletion of MAZR had a mild effect on the generation of CTLs in vitro. However, a transcriptome analysis demonstrated that the combined deletion of MAZR and Runx3 resulted in much more widespread downregulation of CTL signature genes compared to single Runx3 deletion, indicating that MAZR partially compensates for loss of Runx3 in CTLs. Moreover, in line with the findings made in vitro, the analysis of CTL responses to LCMV infection revealed that MAZR and Runx3 cooperatively regulate the expression of CD8 alpha, Granzyme B and perforin in vivo. Interestingly, while memory T cell differentiation is severely impaired in Runx3-deficient mice, the deletion of MAZR leads to an enlargement of the long-lived memory subset and also partially restored the differentiation defect caused by loss of Runx3. This indicates distinct functions of MAZR and Runx3 in the generation of memory T cell subsets, which is in contrast to their cooperative roles in CTLs. Together, our study demonstrates complex interplay between MAZR and Runx3 during CTL and memory T cell differentiation, and provides further insight into the molecular mechanisms underlying the establishment of CTL and memory T cell pools.
Kokoelmat
- Rinnakkaistallenteet [19206]