Nonobese diabetic (NOD) mice are a widely used animal model to study mechanisms leading to autoimmune diabetes. A gluten-free diet reduces and delays the incidence of diabetes in NOD mice, but the underlying mechanisms remain largely unknown. In this study, we performed single-cell transcriptomic and flow cytometry analysis of T cells and innate lymphocytes in the spleen and pancreatic lymph nodes of NOD mice fed a gluten-free or standard diet. We observed that the gluten-free diet did not induce a substantial alteration in the abundance or phenotype of any lymphocyte subset that would directly explain its protective effect against diabetes. However, the gluten-free diet induced subtle changes in the differentiation of subsets with previously proposed protective roles in diabetes development, such as Tregs, activated γδT cells, and NKT cells. Globally, the gluten-free diet paradoxically promoted activation and effector differentiation across multiple subpopulations and induced genes regulated by IL-2, IL-7, and IL-15. In contrast, the standard diet induced type I interferon-responsive genes. Overall, the gluten-free diet might prevent diabetes in NOD mice by inducing small-scale changes in multiple cell types rather than acting on a specific lymphocyte subset.

• Klíčová slova
• NOD mice, T regulatory cells, gluten‐free diet, single‐cell transcriptomics, type I diabetes,
• MeSH
• aktivace lymfocytů imunologie   MeSH
• bezlepková dieta * MeSH
• buněčná diferenciace MeSH
• diabetes mellitus 1. typu * imunologie   MeSH
• myši inbrední NOD MeSH
• myši MeSH
• T-lymfocyty - podskupiny * imunologie   MeSH
• transkriptom MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Microbiome research has gained much attention in recent years as the importance of gut microbiota in regulating host health becomes increasingly evident. However, the impact of radiation on the microbiota in the murine bone marrow transplantation model is still poorly understood. In this paper, we present key findings from our study on how radiation, followed by bone marrow transplantation with or without T cell depletion, impacts the microbiota in the ileum and caecum. Our findings show that radiation has different effects on the microbiota of the two intestinal regions, with the caecum showing increased interindividual variation, suggesting an impaired ability of the host to regulate microbial symbionts, consistent with the Anna Karenina principle. Additionally, we observed changes in the ileum composition, including an increase in bacterial taxa that are important modulators of host health, such as Akkermansia and Faecalibaculum. In contrast, radiation in the caecum was associated with an increased abundance of several common commensal taxa in the gut, including Lachnospiraceae and Bacteroides. Finally, we found that high doses of radiation had more substantial effects on the caecal microbiota of the T-cell-depleted group than that of the non-T-cell-depleted group. Overall, our results contribute to a better understanding of the complex relationship between radiation and the gut microbiota in the context of bone marrow transplantation and highlight the importance of considering different intestinal regions when studying microbiome responses to environmental stressors.

• Klíčová slova
• BM transplantation, HSC, T cell depleted, T cell replete, microbiome and dysbiosis,
• Publikační typ
• časopisecké články MeSH

In most mammals, conspecific chemosensory communication relies on semiochemical release within complex bodily secretions and subsequent stimulus detection by the vomeronasal organ (VNO). Urine, a rich source of ethologically relevant chemosignals, conveys detailed information about sex, social hierarchy, health, and reproductive state, which becomes accessible to a conspecific via vomeronasal sampling. So far, however, numerous aspects of social chemosignaling along the vomeronasal pathway remain unclear. Moreover, since virtually all research on vomeronasal physiology is based on secretions derived from inbred laboratory mice, it remains uncertain whether such stimuli provide a true representation of potentially more relevant cues found in the wild. Here, we combine a robust low-noise VNO activity assay with comparative molecular profiling of sex- and strain-specific mouse urine samples from two inbred laboratory strains as well as from wild mice. With comprehensive molecular portraits of these secretions, VNO activity analysis now enables us to (i) assess whether and, if so, how much sex/strain-selective 'raw' chemical information in urine is accessible via vomeronasal sampling; (ii) identify which chemicals exhibit sufficient discriminatory power to signal an animal's sex, strain, or both; (iii) determine the extent to which wild mouse secretions are unique; and (iv) analyze whether vomeronasal response profiles differ between strains. We report both sex- and, in particular, strain-selective VNO representations of chemical information. Within the urinary 'secretome', both volatile compounds and proteins exhibit sufficient discriminative power to provide sex- and strain-specific molecular fingerprints. While total protein amount is substantially enriched in male urine, females secrete a larger variety at overall comparatively low concentrations. Surprisingly, the molecular spectrum of wild mouse urine does not dramatically exceed that of inbred strains. Finally, vomeronasal response profiles differ between C57BL/6 and BALB/c animals, with particularly disparate representations of female semiochemicals.

• Klíčová slova
• biochemistry, chemical biology, chemosensory system, chemosignaling, mouse, neuroscience, olfaction, vomeronasal organ, vomeronasal sensory neurons,
• MeSH
• feromony moč   metabolismus   MeSH
• inbrední kmeny myší MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• odoranty analýza   MeSH
• vomeronazální orgán * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The gut microbiota of vertebrates is acquired from the environment and other individuals, including parents and unrelated conspecifics. In the laboratory mouse, a key animal model, inter-individual interactions are severely limited and its gut microbiota is abnormal. Surprisingly, our understanding of how inter-individual transmission impacts house mouse gut microbiota is solely derived from laboratory experiments. We investigated the effects of inter-individual transmission on gut microbiota in two subspecies of house mice (Mus musculus musculus and M. m. domesticus) raised in a semi-natural environment without social or mating restrictions. We assessed the correlation between microbiota composition (16S rRNA profiles), social contact intensity (microtransponder-based social networks), and mouse relatedness (microsatellite-based pedigrees). Inter-individual transmission had a greater impact on the lower gut (colon and cecum) than on the small intestine (ileum). In the lower gut, relatedness and social contact independently influenced microbiota similarity. Despite female-biased parental care, both parents exerted a similar influence on their offspring's microbiota, diminishing with the offspring's age in adulthood. Inter-individual transmission was more pronounced in M. m. domesticus, a subspecies, with a social and reproductive network divided into more closed modules. This suggests that the transmission magnitude depends on the social and genetic structure of the studied population.

• Klíčová slova
• gastrointestinal tract, inter-individual transmission, microbiome, relatedness, social contact,
• MeSH
• Bacteria genetika   klasifikace   izolace a purifikace   MeSH
• mikrosatelitní repetice MeSH
• myši MeSH
• RNA ribozomální 16S * genetika   MeSH
• střevní mikroflóra * genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• RNA ribozomální 16S * MeSH

Symbiotic microbial communities affect the host immune system and produce molecules contributing to the odor of an individual. In many mammalian species, saliva and vaginal fluids are important sources of chemical signals that originate from bacterial metabolism and may act as honest signals of health and reproductive status. In this study, we aimed to define oral and vaginal microbiomes and their dynamics throughout the estrous cycle in wild house mice. In addition, we analyzed a subset of vaginal proteomes and metabolomes to detect potential interactions with microbiomes. 16S rRNA sequencing revealed that both saliva and vagina are dominated by Firmicutes and Proteobacteria but differ at the genus level. The oral microbiome is more stable during the estrous cycle and most abundant bacteria belong to the genera Gemella and Streptococcus, while the vaginal microbiome shows higher bacterial diversity and dynamics during the reproductive cycle and is characterized by the dominance of Muribacter and Rodentibacter. These two genera cover around 50% of the bacterial community during estrus. Proteomic profiling of vaginal fluids revealed specific protein patterns associated with different estrous phases. Highly expressed proteins in estrus involve the keratinization process thus providing estrus markers (e.g., Hrnr) while some proteins are downregulated such as immune-related proteins that limit bacterial growth (Camp, Clu, Elane, Lyz2, and Ngp). The vaginal metabolome contains volatile compounds potentially involved in chemical communication, for example, ketones, aldehydes, and esters of carboxylic acids. Data integration of all three OMICs data sets revealed high correlations, thus providing evidence that microbiomes, host proteomes, and metabolomes may interact.IMPORTANCEOur data revealed dynamic changes in vaginal, but not salivary, microbiome composition during the reproductive cycle of wild mice. With multiple OMICs platforms, we provide evidence that changes in microbiota in the vaginal environment are accompanied by changes in the proteomic and metabolomics profiles of the host. This study describes the natural microbiota of wild mice and may contribute to a better understanding of microbiome-host immune system interactions during the hormonal and cellular changes in the female reproductive tract. Moreover, analysis of volatiles in the vaginal fluid shows particular substances that can be involved in chemical communication and reproductive behavior.

• Klíčová slova
• 16S RNA sequencing, Mus musculus, Pasteurellaceae, estrous cycle, estrus, microbiome, oral, proteome, saliva, vaginal,
• MeSH
• Bacteria genetika   MeSH
• estrální cyklus MeSH
• myši MeSH
• proteiny intermediálních filament MeSH
• proteiny vázající vápník MeSH
• proteom * MeSH
• proteomika * MeSH
• RNA ribozomální 16S genetika   MeSH
• rozmnožování MeSH
• savci MeSH
• vagina mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Hrnr protein, mouse MeSH Prohlížeč
• proteiny intermediálních filament MeSH
• proteiny vázající vápník MeSH
• proteom * MeSH
• RNA ribozomální 16S MeSH

Arthroderma is the most diverse genus of dermatophytes, and its natural reservoir is considered to be soil enriched by keratin sources. During a study on the diversity of dermatophytes in wild small rodents in the Czech Republic, we isolated several strains of Arthroderma. To explore the diversity and ecological significance of these isolates from rodents (n = 29), we characterised the strains genetically (i.e., sequenced ITS, tubb and tef1α), morphologically, physiologically, and by conducting mating experiments. We then compared the rodent-derived strains to existing ITS sequence data from GenBank and the GlobalFungi Database to further investigate biogeography and the association of Arthroderma species with different types of environments. In total, eight Arthroderma species were isolated from rodents, including four previously described species (A. crocatum, A. cuniculi, A. curreyi, A. quadrifidum) and four new species proposed herein, i.e., A. rodenticum, A. simile, A. zoogenum and A. psychrophilum. The geographical distribution of these newly described species was not restricted to the Czech Republic nor rodents. Additional isolates were obtained from bats and other mammals, reptiles, and soil from Europe, North America, and Asia. Data mining showed that the genus has a diverse ecology, with some lineages occurring relatively frequently in soil, whereas others appeared to be more closely associated with live animals, as we observed in A. rodenticum. Low numbers of sequence reads ascribed to Arthroderma in soil show that the genus is rare in this environment, which supports the hypothesis that Arthroderma spp. are not soil generalists but rather strongly associated with animals and keratin debris. This is the first study to utilise existing metabarcoding data to assess biogeographical, ecological, and diversity patterns in dermatophytes. Citation: Moulíková Š, Kolařík M, Lorch JM, et al. 2022. Wild rodents harbour high diversity of Arthroderma. Persoonia 50: 27- 47. https://doi.org/10.3767/persoonia.2023.50.02.

• Klíčová slova
• Arthroderma, GlobalFungi, geophilic dermatophytes, mating type genes, new taxa, polyphasic taxonomy, wild rodents,
• Publikační typ
• časopisecké články MeSH

In most mammals and particularly in mice, chemical communication relies on the detection of ethologically relevant fitness-related cues from other individuals. In mice, urine is the primary source of these signals, so we employed proteomics and metabolomics to identify key components of chemical signalling. We show that there is a correspondence between urinary volatiles and proteins in the representation of genetic background, sex and environment in two house mouse subspecies Mus musculus musculus and M. m. domesticus. We found that environment has a strong influence upon proteomic and metabolomic variation and that volatile mixtures better represent males while females have surprisingly more sex-biased proteins. Using machine learning and combined-omics techniques, we identified mixtures of metabolites and proteins that are associated with biological features.

• MeSH
• genetická variace MeSH
• myši MeSH
• podněty MeSH
• proteiny * MeSH
• proteomika * MeSH
• savci MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• proteiny * MeSH

The kinase LCK and CD4/CD8 co-receptors are crucial components of the T cell antigen receptor (TCR) signaling machinery, leading to key T cell fate decisions. Despite decades of research, the roles of CD4-LCK and CD8-LCK interactions in TCR triggering in vivo remain unknown. In this study, we created animal models expressing endogenous levels of modified LCK to resolve whether and how co-receptor-bound LCK drives TCR signaling. We demonstrated that the role of LCK depends on the co-receptor to which it is bound. The CD8-bound LCK is largely dispensable for antiviral and antitumor activity of cytotoxic T cells in mice; however, it facilitates CD8+ T cell responses to suboptimal antigens in a kinase-dependent manner. By contrast, the CD4-bound LCK is required for efficient development and function of helper T cells via a kinase-independent stabilization of surface CD4. Overall, our findings reveal the role of co-receptor-bound LCK in T cell biology, show that CD4- and CD8-bound LCK drive T cell development and effector immune responses using qualitatively different mechanisms and identify the co-receptor-LCK interactions as promising targets for immunomodulation.

• MeSH
• antigeny CD4 MeSH
• antigeny CD8 metabolismus   MeSH
• cytotoxické T-lymfocyty * metabolismus   MeSH
• myši MeSH
• receptory antigenů T-buněk metabolismus   MeSH
• signální transdukce MeSH
• tyrosinkinasa p56(lck), specifická pro lymfocyty * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• antigeny CD4 MeSH
• antigeny CD8 MeSH
• receptory antigenů T-buněk MeSH
• tyrosinkinasa p56(lck), specifická pro lymfocyty * MeSH

Interleukin-17A (IL-17A) is a key mediator of protective immunity to yeast and bacterial infections but also drives the pathogenesis of several autoimmune diseases, such as psoriasis or psoriatic arthritis. Here we show that the tetra-transmembrane protein CMTM4 is a subunit of the IL-17 receptor (IL-17R). CMTM4 constitutively associated with IL-17R subunit C to mediate its stability, glycosylation and plasma membrane localization. Both mouse and human cell lines deficient in CMTM4 were largely unresponsive to IL-17A, due to their inability to assemble the IL-17R signaling complex. Accordingly, CMTM4-deficient mice had a severe defect in the recruitment of immune cells following IL-17A administration and were largely resistant to experimental psoriasis, but not to experimental autoimmune encephalomyelitis. Collectively, our data identified CMTM4 as an essential component of IL-17R and a potential therapeutic target for treating IL-17-mediated autoimmune diseases.

• MeSH
• encefalomyelitida autoimunitní experimentální * genetika   MeSH
• interleukin-17 metabolismus   MeSH
• lidé MeSH
• myši MeSH
• proteiny obsahující MARVEL doménu genetika   MeSH
• psoriatická artritida * MeSH
• psoriáza * MeSH
• receptory interleukinu-17 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CMTM4 protein, human MeSH Prohlížeč
• interleukin-17 MeSH
• proteiny obsahující MARVEL doménu MeSH
• receptory interleukinu-17 MeSH

Mature T cells are selected for recognizing self-antigens with low to intermediate affinity in the thymus. Recently, the relative differences in self-reactivity among individual T-cell clones were appreciated as important factors regulating their fate and immune response, but the role of self-reactivity in T-cell biology is incompletely understood. We addressed the role of self-reactivity in T-cell diversity by generating an atlas of mouse peripheral CD8+ T cells, which revealed two unconventional populations of antigen-inexperienced T cells. In the next step, we examined the steady-state phenotype of monoclonal T cells with various levels of self-reactivity. Highly self-reactive clones preferentially differentiate into antigen-inexperienced memory-like cells, but do not form a population expressing type I interferon-induced genes, showing that these two subsets have unrelated origins. The functional comparison of naïve monoclonal CD8+ T cells specific to the identical model antigen did not show any correlation between the level of self-reactivity and the magnitude of the immune response.

• Klíčová slova
• T cell, T-cell diversity, antigen-inexperienced memory-like CD8 T cells, interferon response, self-reactivity,
• MeSH
• autoantigeny MeSH
• buněčné klony MeSH
• CD8-pozitivní T-lymfocyty * MeSH
• interferon typ I * MeSH
• myši MeSH
• thymus MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoantigeny MeSH
• interferon typ I * MeSH