ZEB2 is a multi-zinc-finger transcription factor known to play a significant role in early neurogenesis and in epithelial-mesenchymal transition-dependent tumor metastasis. Although the function of ZEB2 in T lymphocytes is unknown, activity of the closely related family member ZEB1 has been implicated in lymphocyte development. Here, we find that ZEB2 expression is up-regulated by activated T cells, specifically in the KLRG1(hi) effector CD8(+) T cell subset. Loss of ZEB2 expression results in a significant loss of antigen-specific CD8(+) T cells after primary and secondary infection with a severe impairment in the generation of the KLRG1(hi) effector memory cell population. We show that ZEB2, which can bind DNA at tandem, consensus E-box sites, regulates gene expression of several E-protein targets and may directly repress Il7r and Il2 in CD8(+) T cells responding to infection. Furthermore, we find that T-bet binds to highly conserved T-box sites in the Zeb2 gene and that T-bet and ZEB2 regulate similar gene expression programs in effector T cells, suggesting that T-bet acts upstream and through regulation of ZEB2. Collectively, we place ZEB2 in a larger transcriptional network that is responsible for the balance between terminal differentiation and formation of memory CD8(+) T cells.
Promoting tumor cell senescence arrests the cell cycle of tumor cells and activates the immune system to eliminate these senescent cells, thereby suppressing tumor growth. Nevertheless, PD-L1 positive senescent tumor cells resist immune clearance and possess the ability to secret various cytokines and inflammatory factors that stimulate the growth of tumor cells. Consequently, drugs capable of both triggering senescence in tumor cells and concurrently diminishing the expression of PD-L1 to counteract immune evasion are urgently needed.
Department of Immunology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Toronto General Hospital Research Institute, Ajmera Transplant Centre, University Health Network, Toronto, ON M5G 1L7, Canada. Electronic address:
Interleukin-10 (IL-10)-producing group 2 innate lymphoid cells (ILC2) regulate inflammatory immune responses, yet their therapeutic potential remains largely unexplored. Here, we demonstrate that cell therapy with human ILC2 inhibits pathogenic T cell responses in humanized mouse models of graft-versus-host disease (GVHD), resulting in reduced GVHD severity and improved overall survival without limiting the graft-versus-leukemia effect. ILC2 conferred superior protection from GVHD than IL-10 ILC2s, and blocking IL-10 and IL-4 abrogated ILC2 protective effects, indicating that these cytokines are important for the protective effects of ILC2.
Background: CD4+ T cells expressing α4β7 are optimal targets for HIV infections, with higher pre-HIV α4β7hi expression linked to increased HIV acquisition and progression in South African women. However, similar associations were not observed in men who have sex with men (MSM) or people who inject drugs (PWID) in the Americas, indicating need for further research.
Methods: This retrospective case-control study enrolled heterosexual men and women from South Africa (HIV Vaccine Trials Network; HVTN 503) and East Africa (Partners Pre-Exposure Prophylaxis/Couples' Observational Study; PP/COS), quantifying α4β7 expression on CD4+ T cells as a predictor of subsequent HIV risk using flow cytometry analyses.
Beijing Key Laboratory for HIV/AIDS Research, Sino-French Joint Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.
Human immunodeficiency Virus (HIV) and () co-infection presents a significant public health challenge worldwide. Comprehensive assessment of the immune response in HIV/ co-infection is complex and challenging. CD8T cells play a pivotal role in the adaptive immune response to both HIV and .
HCC cell immune escape is a critical element in the evolution of HCC malignancy. Herein, the regulatory mechanism of lncRNA NEAT1 in regulating HCC immune escape was investigated. Exosomes were isolated from M2 TAMs using ExoQuick-TC.
