TY  - JOUR
A1  - Schütz, Burkhard
A1  - Jurastow, Innokentij
A1  - Bader, Sandra
A1  - Ringer, Cornelia
A1  - Engelhardt, Jakob von
A1  - Chubanov, Vladimir
A1  - Gudermann, Thomas
A1  - Diener, Martin
A1  - Kummer, Wolfgang
A1  - Krasteva-Christ, Gabriela
A1  - Weihe, Eberhard
T1  - Chemical coding and chemosensory properties of cholinergic brush cells in the mouse gastrointestinal and biliary tract
JF  - Frontiers in Physiology
N2  - The mouse gastro-intestinal and biliary tract mucosal epithelia harbor choline acetyltransferase (ChAT)-positive brush cells with taste cell-like traits. With the aid of two transgenic mouse lines that express green fluorescent protein (EGFP) under the control of the ChAT promoter (EGFP\(^{ChAT}\)) and by using in situ hybridization and immunohistochemistry we found that EGFP\(^{ChAT}\) cells were clustered in the epithelium lining the gastric groove. EGFP\(^{ChAT}\) cells were numerous in the gall bladder and bile duct, and found scattered as solitary cells along the small and large intestine. While all EGFP\(^{ChAT}\) cells were also ChAT-positive, expression of the high-affinity choline transporter (ChT1) was never detected. Except for the proximal colon, EGFP\(^{ChAT}\) cells also lacked detectable expression of the vesicular acetylcholine transporter (VAChT). EGFP\(^{ChAT}\) cells were found to be separate from enteroendocrine cells, however they were all immunoreactive for cytokeratin 18 (CK18), transient receptor potential melastatin-like subtype 5 channel (TRPM5), and for cyclooxygenases 1 (COX1) and 2 (COX2). The ex vivo stimulation of colonic EGFP\(^{ChAT}\) cells with the bitter substance denatonium resulted in a strong increase in intracellular calcium, while in other epithelial cells such an increase was significantly weaker and also timely delayed. Subsequent stimulation with cycloheximide was ineffective in both cell populations. Given their chemical coding and chemosensory properties, EGFP\(^{ChAT}\) brush cells thus may have integrative functions and participate in induction of protective reflexes and inflammatory events by utilizing ACh and prostaglandins for paracrine signaling.
KW  - vesicular acetylcholine transporter
KW  - nonneuronal acetylcholine
KW  - nervous system
KW  - functional characterization
KW  - cholinergic
KW  - taste receptor cells
KW  - enteroendocrine cells
KW  - gene locus
KW  - tuft cells
KW  - transgenic mice
KW  - expression
KW  - brush cell
KW  - ChAT
KW  - VAChT
KW  - ChT1
KW  - intestine
KW  - gall bladder
KW  - bile duct
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143550
VL  - 6
IS  - 87
ER  - 
TY  - JOUR
A1  - Luu, Maik
A1  - Schütz, Burkhard
A1  - Lauth, Matthias
A1  - Visekruna, Alexander
T1  - The impact of gut microbiota-derived metabolites on the tumor immune microenvironment
JF  - Cancers
N2  - Prevention of the effectiveness of anti-tumor immune responses is one of the canonical cancer hallmarks. The competition for crucial nutrients within the tumor microenvironment (TME) between cancer cells and immune cells creates a complex interplay characterized by metabolic deprivation. Extensive efforts have recently been made to understand better the dynamic interactions between cancer cells and surrounding immune cells. Paradoxically, both cancer cells and activated T cells are metabolically dependent on glycolysis, even in the presence of oxygen, a metabolic process known as the Warburg effect. The intestinal microbial community delivers various types of small molecules that can potentially augment the functional capabilities of the host immune system. Currently, several studies are trying to explore the complex functional relationship between the metabolites secreted by the human microbiome and anti-tumor immunity. Recently, it has been shown that a diverse array of commensal bacteria synthetizes bioactive molecules that enhance the efficacy of cancer immunotherapy, including immune checkpoint inhibitor (ICI) treatment and adoptive cell therapy with chimeric antigen receptor (CAR) T cells. In this review, we highlight the importance of commensal bacteria, particularly of the gut microbiota-derived metabolites that are capable of shaping metabolic, transcriptional and epigenetic processes within the TME in a therapeutically meaningful way.
KW  - tumor microenvironment (TME)
KW  - commensal bacteria
KW  - intratumoral microbiota
KW  - oncobiome
KW  - microbiota-derived metabolites
KW  - cancer immunotherapy
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311005
SN  - 2072-6694
VL  - 15
IS  - 5
ER  -