The regulatory role and mechanism of Hoxa10 in CD4+ T cells: insights into immunological memory

Memory T cells are a crucial component of the immune system, possessing rapid and long-lasting immune protection. The study of memory T cell formation and function has long been a focal point in immunology research. However, the underlying mechanisms of memory T cells' rapid response to secondary antigenic stimulation remain to be further elucidated. In this study, we uncover the critical role of the transcription factor Hoxa10 in regulating the activation speed of CD4+ memory T cells. We found that Hoxa10 is highly expressed in CD4+ memory T cells, and its deletion impairs the activation speed and strength of these cells. Further investigation revealed that Hoxa10 regulates the transcriptional activity of Dnajb14, stabilizing the protein level of the potassium channel KCNH2 in T cells, thereby reducing calcium influx during activation. Overexpression of Dnajb14 and Kcnh2 can reverse the effect of Hoxa10 deletion on calcium flux in CD4+ T cells. In summary, we elucidate the molecular mechanism by which Hoxa10 regulates the activation of CD4+ memory T cells, providing new insights into the rapid and strong response of memory T cells. This also offers a theoretical basis for understanding and treating clinical conditions involving memory T cells, such as infections, autoimmune diseases and tumors.