Biology subjects

Lemenze, A.

Publications and source records attributed to Lemenze, A..

3 recordsLinked to original sources

bioRxiv2021

Breast tumor IGF-1R regulates cell adhesion and metastasis: Alignment of mouse single cell and human breast cancer transcriptomics

The acquisition of a metastatic phenotype is the critical event that determines patient survival from breast cancer. Several receptor tyrosine kinases have functions both in promoting and inhibiting metastasis in breast tumors. Although the insulin-like growth factor 1 receptor (IGF-1R) has been considered a target for inhibition in breast cancer, low levels of IGF-1R expression are associated with worse overall patient survival. To determine how reduced IGF-1R impacts tumor phenotype, we used weighted gene correlation network analysis (WGCNA) of METABRIC patient data and identified gene modules specific to cell cycle, adhesion, and immune cell signaling inversely correlated with IGF-1R expression in human breast cancers. Integration of human patient data with data from mouse tumors revealed similar pathways necessary for promoting metastasis in basal-like tumors with reduced signaling or expression of the IGF-1R. Functional analyses revealed the basis for the enhanced metastatic phenotype including alterations in E- and P-cadherins.

cancer biology↗

bioRxiv2021

A transmissible γδ intraepithelial lymphocyte hyperproliferative phenotype is associated with the intestinal microbiota and confers protection against acute infection.

Intraepithelial lymphocytes expressing the {gamma}{delta} T cell receptor ({gamma}{delta} IELs) serve as a first line of defense against luminal microbes. Although the presence of an intact microbiota is dispensable for {gamma}{delta} IEL development, several microbial factors contribute to the maintenance of this sentinel population. However, whether specific commensals influence population of the {gamma}{delta} IEL compartment under homeostatic conditions has yet to be determined. We identified a novel {gamma}{delta} IEL hyperproliferative phenotype that arises early in life and is characterized by expansion of multiple V{gamma} subsets. Horizontal transfer of this hyperproliferative phenotype to mice harboring a phenotypically normal {gamma}{delta} IEL compartment was prevented following antibiotic treatment, thus demonstrating that the microbiota is both necessary and sufficient for the observed increase in {gamma}{delta} IELs. Further, we identified a group of unique gut bacteria represented by 5 amplicon sequence variants (ASV) which are strongly associated with {gamma}{delta} IEL expansion. Using intravital microscopy, we find that hyperproliferative {gamma}{delta} IELs also exhibit increased migratory behavior leading to enhanced protection against bacterial infection. These findings reveal that transfer of a specific group of commensals can regulate {gamma}{delta} IEL homeostasis and immune surveillance, which may provide a novel means to reinforce the epithelial barrier.

immunology↗

bioRxiv2020

Monocyte-derived alveolar macrophages mediate resistance to migrating helminths through depletion of arginine availability

Macrophages are known to mediate anti-helminth responses, but it remains uncertain which subsets are involved or how macrophages actually kill helminths. Here we show rapid monocyte recruitment to the lung after infection with the nematode parasite, Nippostrongylus brasiliensis. In this inflamed tissue microenvironment these monocytes differentiate into an alveolar-like macrophage (AM) phenotype, expressing both Siglec-F and CD11c, surround invading parasitic larvae and preferentially kill parasites in vitro. Monocyte-derived AMs (Mo-AMs) express type 2-associated markers and show distinct remodeling of the chromatin landscape relative to tissue-derived AMs. In particular, they express high amounts of Arg1 (arginase-1), which we demonstrate mediates helminth killing through L-arginine depletion. These studies indicate that recruited monocytes are selectively programmed in the pulmonary environment to express AM markers and an anti-helminth phenotype.

immunology↗