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Hoffmann, M. H.

Publications and source records attributed to Hoffmann, M. H..

4 recordsLinked to original sources

Alternatively polarized neutrophils metabolically restrain macrophage-driven inflammation

Macrophage-driven inflammation underlies many inflammatory diseases, yet the mechanisms that restrain macrophage activation within inflamed tissues remain poorly understood. Using mouse models of foreign body granuloma formation and macrophage activation syndrome, we show that neutrophils accumulate at sites of inflammation and metabolically restrain macrophage-driven pathology. Neutrophil depletion or genetic impairment exacerbated tissue pathology, whereas induced neutrophilia attenuated inflammatory damage. Tissue-infiltrating neutrophils acquired an alternatively polarized state characterized by high arginase 1 activity that was regulated by an IL4Ra-STAT3-NOX2 signaling axis. Functionally, polarized neutrophils depleted extracellular arginine in an arginase 1-dependent manner, thereby limiting macrophage effector programs. Human neutrophils exhibited conserved regulation of arginase activity, and alternatively polarized neutrophils were detected in patients with sarcoidosis and macrophage activation syndrome. Together, these findings identify an arginine-dependent metabolic mechanism through which alternatively polarized neutrophils restrain macrophage-driven inflammation and reveal a previously unrecognized immune-regulatory role for these cells in chronic inflammatory disease.

immunology↗

Distinct genomic architectures but the same gene underlie the convergent evolution of a plant supergene

AO_SCPLOWBSTRACTC_SCPLOWEvolution reflects a balance between innovation and constraint, often repurposing existing components in new contexts. Convergent evolution exemplifies this interplay, with similar traits evolving independently in different species, yet the genomic mechanisms enabling such repeatability remain poorly understood. Here, by analyzing ten chromosome-scale genome assemblies, including seven newly generated, we discovered that the S-locus supergene (a cluster of tightly linked genes controlling a floral dimorphism called distyly) arose independently multiple times within the primrose family, Darwins iconic system for studying distyly. In each case, the same gene was independently duplicated and co-opted, yet the resulting genomic architectures differed, ranging from hemizygous (present on one chromosome copy) to heterozygous (on both copies). These diverse architectures shaped supergene evolution differently, with genetic degeneration occurring only in the heterozygous case. By uncovering multiple mechanisms for supergene origins, our work shows how convergent evolution can produce similar phenotypes by reusing the same genetic building blocks while exploring distinct genomic configurations.

evolutionary biology↗

Macrophages foster adaptive anti-tumor immunity by ZEB1-dependent cytotoxic T cell chemoattraction

Tumor-associated macrophages (TAMs) shape the tumor microenvironment (TME) and exert a decisive impact on anti-tumor immunity. Understanding TAM function is therefore critical to understand anti-tumor immune responses and to design immunotherapies. Here, we describe the transcription factor ZEB1, a well-known driver of epithelial-to-mesenchymal transition, as an intrinsic regulator of TAM function in adaptive anti-tumor immunity. By combining cell type-specific deletion of Zeb1 with syngeneic models of colorectal and pancreatic cancer, we discovered an unexpected function of ZEB1 in the TAM-mediated control of T cell trafficking. ZEB1 supports secretion of a subset of chemokines including CCL2 and CCL22 by promoting their transcription and translation as well as by safeguarding protein processing. ZEB1 thereby elevates cytotoxic T cell (CTL) recruitment in vitro and in vivo and fosters immunosurveillance during tumor as well as lung metastatic outgrowth. Our study spotlights ZEB1 as a crucial facilitator of adaptive anti-tumor immunity and uncovers a potential therapeutic window of opportunity for cytokine-guided enhancement of CTL infiltration into tumors and metastases.

cancer biology↗

Phylogeny, morphology and the role of hybridization as driving force of evolution in grass tribes Aveneae and Poeae (Poaceae)

To investigate the evolutionary diversification and morphological evolution of grass supertribe Poodae (subfam. Pooideae, Poaceae) we conducted a comprehensive molecular phylogenetic analysis including representatives from most of their accepted genera. We focused on generating a DNA sequence dataset of plastid matK gene-3trnK exon and trnL- trnF regions and nuclear ribosomal ITS1-5.8S gene-ITS2 and ETS that was taxonomically overlapping as completely as possible (altogether 257 species). The idea was to infer whether phylogenetic trees or certain clades based on plastid and nuclear DNA data correspond with each other or discord, revealing signatures of past hybridization. The datasets were analysed using maximum parsimony, maximum likelihood and Bayesian approaches. Instances of severe conflicts between the phylogenetic trees derived from both datasets, some of which have been noted earlier, unambiguously point to hybrid origin of several lineages (subtribes, groups of genera, sometimes genera) such as Phalaridinae, Scolochloinae, Sesleriinae, Torreyochloinae; Arctopoa, Castellia, Graphephorum, Hyalopodium, Lagurus, Macrobriza, Puccinellia plus Sclerochloa, Sesleria, Tricholemma, American Trisetum, etc. and presumably Airinae, Holcinae and Phleinae. Calamagrostis flavens appears to be an intergeneric hybrid between Agrostis and Calamagrostis. Most frequently there is good agreement of other regions of the trees, apart from intrinsic different phylogenetic resolution of the respective DNA markers. To explore the to date rather unclear morphological evolution of our study group a data matrix encompassing finally 188 characters was analysed for ancestral state reconstructions (ASR) using the tree from the combined molecular dataset as presumably best approximation to the species phylogeny. For 74 characters ASRs were feasible and yielded partly surprising results for the study group as a whole but also for some of their subdivisions. Considering taxonomy and classification it became evident, that many morphological characters show a very high degree of homoplasy and are seemingly able to change within comparatively short timespans in the evolution of our grasses. Most of the taxonomic units distinguished within our study group, e.g. as subtribes, are defined less by consistent morphological characters or character combinations and should be rather understood as clades revealed by molecular phylogenetic analysis. One reason for this extreme homoplasy concerning traditionally highly rated characters of inflorescences or spikelets and their components might be that they have little to do with pollination (always wind) or adaptation to pollinators as in other angiosperms but rather with dispersal and diaspores. Easily changing structure of spikelet disarticulation, of glume, lemma or awn characters might be advantageous in the rapid adaptation to different habitats and micro-habitats, which was evidently most successfully accomplished by these grasses. A partly revised classification of Poodae is presented, including a re-instatement of tribes Aveneae and Poeae s.str. Following a comparatively narrow delineation of preferably monophyletic subtribes, Antinoriinae, Avenulinae, Brizochloinae, Helictochloinae, Hypseochloinae are described as new. New genera are Arctohyalopoa and Hyalopodium. New combinations are Arctohyalopoa lanatiflora, A. lanatiflora subsp. ivanoviae, A. lanatiflora subsp. momica, Colpodium biebersteinianum, C. kochii, C. trichopodum, C. verticillatum, Deschampsia micrathera, Dupontia fulva, Festuca masafuerana, Hyalopodium araraticum, Paracolpodium baltistanicum, Parapholis cylindrica, P. xpauneroi. Festuca masatierrae is a new name.\n\nSupporting Information may be found online in the Supporting Information section at the end of the article.

plant biology↗