bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 4, 2024
The ovary is one of the first organs to exhibit signs aging, characterized by reduced tissue function, chronic inflammation, and fibrosis. Multinucleated giant cells (MNGCs), formed macrophage fusion, typically occur in immune pathologies, including infectious non-infectious granulomas foreign body response
Language: Английский
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown
Published: Feb. 21, 2023
Cancer immunotherapy offers lifesaving treatments for cancers, but the lack of reliable preclinical models that could enable mechanistic studies tumor-immune interactions hampers identification new therapeutic strategies. We hypothesized 3D confined microchannels, formed by interstitial space between bio-conjugated liquid-like solids (LLS), CAR T dynamic locomotion within an immunosuppressive TME to carry out anti-tumor function. Murine CD70-specific cells cocultured with CD70-expressing glioblastoma and osteosarcoma demonstrated efficient trafficking, infiltration, killing cancer cells. The activity was clearly captured via longterm in situ imaging supported upregulation cytokines chemokines including IFNg, CXCL9, CXCL10, CCL2, CCL3, CCL4. Interestingly, target cells, upon immune attack, initiated "immune escape" response frantically invading surrounding microenvironment. This phenomenon however not observed wild-type tumor samples which remained intact produced no relevant cytokine response. Single collection transcriptomic profiling at regions interest revealed feasibility identifying differential gene expression amongst subpopulations. Complimentary vitro platforms are necessary uncover biology mechanisms, as emphasized significant roles its heterogeneity.
Language: Английский
Citations
4
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown
Published: July 17, 2023
The optimal residue identity at each position in a protein is determined by its structural, evolutionary, and functional context. We seek to learn the representation space of amino-acid different structural contexts proteins. Inspired masked language modeling (MLM), our training aims transduce learning labels from non-masked residues their environments general (e.g., protein) specific interface or antibody complex). Our results on native sequence recovery forward folding with AlphaFold2 suggest that amino acid label for may be context alone (i.e., without knowledge surrounding residues). further find sampled models recapitulate evolutionary neighborhood wildtype sequence. Remarkably, sequences conditioned highly plastic structures conformational flexibility encoded structures. Furthermore, maximum-likelihood interfaces designed binding energies wide range strengths. also propose compare fine-tuning strategies train designing CDR loops antibodies antibody-antigen leveraging databases proteins, (synthetic experimental) protein-protein complexes. show pretraining more improves loops, especially hypervariable H3, while helps preserve patterns observed special contexts.
Language: Английский
Citations
4
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: July 3, 2024
Abstract Background and Aims Accumulating evidence suggests the microbiota is a key factor in disorders of gut-brain interaction (DGBI), by affecting host immune neural systems. However, underlying mechanisms remain elusive due to their complexity clinical heterogeneity patients with DGBIs. We aimed identify neuroimmune pathways that are critical microbiota-gut-brain communication during de novo gut colonization. Methods employed combination gnotobiotic state-of-the-art microbial tools, behavioral analysis, pharmacological approaches. Germ-free wild type, MyD88 −/− Ticam1 SCID mice were studied before after colonization specific pathogen-free microbiota, Altered Schaedler Flora, E. coli or S. typhimurium (permanent transient colonizers). TLR agonists antagonists, CCR7 antagonist immunomodulators used study pathways. assessed brain c-Fos, brain-derived neurotrophic factor, dendritic glial cells immunofluorescence, expression genes NanoString performed proteomics. Results Bacterial monocolonization, conventionalization administration products germ-free altered mouse behavior similarly, acting through Toll-like receptor nucleotide-binding oligomerization domain signaling. The process required CD11b + CD11c CD103 cell activation migration into brain. change did not require continued presence bacteria was associated multiple neuro-immune networks Conclusions Changes plasticity occur rapidly upon initial involve innate signaling brain, mediated migration. results new target therapeutic potential for DGBIs developing context increased blood-brain barrier permeability. Highlights Microbiota impairment (DGBI) Microbial induces changes via immunity activates Behavioral
Language: Английский
Citations
1
Clinical & Experimental Immunology, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 5, 2024
Abstract Systemic sclerosis (SSc) is considered a rare autoimmune disease in which there are alterations of both the innate and adaptive immune response resulting production autoantibodies. Abnormalities system compromise normal function blood vessels leading to vasculopathy manifested by Raynaud’s phenomenon, an early sign SSc . As consequence this reactive picture, can evolve tissue fibrosis. Several SSc-specific autoantibodies currently known associated with specific clinical manifestations prognosis. Although pathogenetic role these still unclear, their B cells plasma suggests importance development SSc. This review narratively examines B-cell dysfunctions pathogenesis discusses B-cell-targeted therapies used or potentially useful for management end-organ complications.
Language: Английский
Citations
1
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 4, 2024
The ovary is one of the first organs to exhibit signs aging, characterized by reduced tissue function, chronic inflammation, and fibrosis. Multinucleated giant cells (MNGCs), formed macrophage fusion, typically occur in immune pathologies, including infectious non-infectious granulomas foreign body response
Language: Английский
Citations
1