The study revealed the mechanism by which PDK1, a protein kinase, regulates Tfh cell differentiation

The eLife journal published a research paper online by the Shuyang Research Group of the School of Biology of China Agricultural University, entitled The Kinase PDK1 is critical for the development of T follicular helper cell solution.
this paper, based on PY3K downstream protein kinase PDK1 (serine/threonine kinase 3-phosphoinositide-dependent kin proteinase 1) condition knockout mice, combined with a variety of genetically engineered mouse models of the immune response analysis, expounded the function of PDK1 in the TFH cell differentiation process and related molecular mechanisms, and further improved the PY3K path in Tfh cell differentiation.
Follicular Helper cell; Tfh is a special sub-group of CD4 plus T cells that promotes and sustains germinal centers and promotes the formation of high-affinity class-converted antibodies, long-lived plasma cells, and memory B cells.
, Tfh cells are critical to the successful production of long-term soytic immunity and memory response to vaccination or infection.
although pi3K-mediated signal path path is known to play an important role in the differentiation of Tfh cells, its fine regulatory mechanism needs to be further improved.
study found that knocking out PDK1 in T cells, whether under acute viral infection or protein immunity, led to significant reduction in Tfh cells in mice and a reduced response to the birth center.
further, by constructing a mouse model of bone marrow chimosa, it is revealed that PDK1 has an effect on the regulation of Tfh cells as an endogenetic cytostic.
using cell step-by-step models and timed targeted induced deletion methods, the researchers found that PDK1 was essential not only for the proliferation and differentiation of early Tfh cells, but also for the maintenance of late Tfh cells.
mechanisms, the researchers found that PDK1 regulates Tfh cell differentiation and relies on upstream ICOS signals.
RNA-seq further reveals that the absence of PDK1 affects the transcription spectrum of Tfh cells, and a series of genes associated with Tfh cell differentiation are significantly affected.
the absence of PDK1, the expression of mTORC1 and downstream Hif1 alpha and p-STAT3S727 decreased, while the absence of PDK1 also led to a decrease in p-AKTS473 and downstream GSK3 beta activity.
these factors together lead to a reduction in the expression of the transcription factor TCF1, further weakening Tfh cell differentiation.
further experiments have confirmed that both the expression TCF1 and STAT3-CA (continuously activated) can correct defects in Tfh cell differentiation.
study reveals that PDK1 activates the extension and phosphorylation levels of genes associated with Tfh cells by directly and indirectly regulating multiple T cell activations that rely on mTORC1 and mTORC2 activity, among which the regulation of TCF1 expression levels is a major regulatory mechanism affecting Tfh cell differentiation.
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