A5024904898- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- CAR-T cell therapy research
- IL-33, ST2, and ILC Pathways
- Sphingolipid Metabolism and Signaling
- Immune Response and Inflammation
- Erythrocyte Function and Pathophysiology
- Adipose Tissue and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Cytomegalovirus and herpesvirus research
- Epigenetics and DNA Methylation
- Immunotherapy and Immune Responses
- Cancer, Lipids, and Metabolism
- Ferroptosis and cancer prognosis
- Cancer Immunotherapy and Biomarkers
- Exercise and Physiological Responses
- HIV Research and Treatment
- Adenosine and Purinergic Signaling
German Cancer Research Center
2018-2024
Heidelberg University
2018-2024
CD4 + regulatory T (T reg ) cells accumulate in the tumor microenvironment (TME) and suppress immune system. Whether how metabolite availability TME influences cell differentiation is not understood. Here, we measured 630 metabolites found that serine palmitic acid, substrates required for synthesis of sphingolipids, were enriched. A serine-free diet or a deficiency Sptlc2, rate-limiting enzyme catalyzing sphingolipid synthesis, suppressed accumulation inhibited growth. Sphinganine, an...
T cell factor 1 (Tcf1) promotes the central memory CD8+ (TCM) differentiation and stemness in lymphoid tissues after systemic infections. It remains unclear whether Tcf1 regulates CD103high tissue-resident (TRM) formation non-lymphoid mucosal We find that is progressively decreased during lung TRM formation. Abrogation of transforming growth β (TGF-β) signaling associated with a loss CD103+ reciprocal gain Tcf1+ cells among precursors vivo. T-cell-specific ablation Tcf7 enhances CD103...
T cells become functionally exhausted in tumors, limiting cell-based immunotherapies. Although several transcription factors regulating the (Tex) cell differentiation are known, comparatively little is known about regulators of Tex survival. Here, we reported that regulator G protein signaling 16 (Rgs-16) suppressed survival tumors. By performing lineage tracing using reporter mice which mCherry marked Rgs16-expressing cells, identified Rgs16+CD8+ tumor-infiltrating lymphocytes (TILs) were...
CD8+ T cells become functionally impaired or "exhausted" in chronic infections, accompanied by unwanted body weight reduction and muscle mass loss. Whether regulates cell exhaustion remains incompletely understood. We report that mouse skeletal increased interleukin (IL)-15 production during LCMV clone 13 infection. Muscle-specific ablation of Il15 enhanced the phenotype. Muscle-derived IL-15 was required to maintain a population CD8+CD103+ muscle-infiltrating lymphocytes (MILs). MILs...
Abstract The malate shuttle is traditionally understood to maintain NAD + /NADH balance between the cytosol and mitochondria. Whether has additional functions unclear. Here we show that chronic viral infections induce CD8 T cell expression of GOT1, a central enzyme in shuttle. Got1 deficiency decreased ratio limited antiviral responses infection; however, increasing did not restore responses. reduced production ammonia scavenger 2-ketoglutarate (2-KG) from glutaminolysis led toxic...
Abstract After recognizing its ligand lipopolysaccharide, Toll-like receptor 4 (TLR4) recruits adaptor proteins to the cell membrane, thereby initiating downstream signaling and triggering inflammation. Whether this recruitment of is dependent solely on protein-protein interactions unknown. Here, we report that sphingolipid sphinganine physically interacts with MyD88 TIRAP promotes in macrophages. Myeloid cell-specific deficiency serine palmitoyltransferase long chain base subunit 2 , which...
Memory CD8+ T cells mature after antigen clearance and ultimately express CD8 protein at levels higher than those detected in effector cells. However, it is not clear whether engagement of the absence antigenic stimulation will result functional activation Here, we found that antibody-mediated memory triggered cell receptor (TCR) downstream signaling, enhanced cell-mediated cytotoxicity promoted cytokine production a glucose- glutamine-dependent manner. Furthermore, pretreatment with an...
While the immunosuppressive function of regulatory T (Treg) cells has been extensively studied, their immune-supportive roles have less well investigated. Using a lymphocytic choriomeningitis virus (LCMV) Armstrong infection mouse model, we found that Treg cell-derived interleukin (IL)-15 is required for long-term maintenance KLRG1+ IL-7Rα- CD62L- terminal effector memory CD8+ (tTEM) cell subset, but dispensable suppressive themselves. In contrast, deletion Il15 from other sources, including...
In noncancerous tissues, neighboring cells coexist in metabolic harmony. This harmony is disrupted cancerous often accompanied by genetic mutations. Tumor fundamentally change the metabolite profiles tumor microenvironment to favor their own growth. this review, we will discuss several examples which mutations reprogram cell pathways, leading consumption of essential nutrients microenvironment, production toxic byproducts, and suppression antitumor immune fitness tumor-killing function....
Abstract The tumor microenvironment (TME) is enriched in various lipid species that are detrimental to anti-tumor T cell function. However, intratumoral CD8+ cells were recently shown require free fatty acids, which also abundant the TME, for survival and It not clear whether these acids regulate transcription or serve as an energy source either directly through a triacylglyerol (TAG) intermediate step (as memory cells). Here, we generated mice with cell-specific deletion of Dgat1, enzyme...