Biology subjects

Giordano, C.

Publications and source records attributed to Giordano, C..

5 recordsLinked to original sources

bioRxiv2026

ClonoDynamics enables replicate-resolved inference of longitudinal T cell receptor repertoire dynamics

Longitudinal T cell receptor repertoire analysis can confound biological change with measurement noise and estimator-induced structure. We developed ClonoDynamics, a framework integrating latent abundance inference with replicate-decoupled estimates of directional change and cross-replicate displacement covariance. Pseudo longitudinal series assembled from 12 independently processed technical measurements of one biological sample revealed apparent restoring dynamics caused by reusing measurements for conditioning and change estimation. Separating these roles between replicates largely removed this artifact. Synthetic controls preserving empirical detection patterns showed dose-dependent recovery of temporal accumulation, resolving the two larger imposed effects but not the smallest. Applied to TCR{beta} repertoires from ten healthy adults sampled weekly for six weeks, ClonoDynamics identified abundance-dependent directional change and shared fluctuations exceeding the technical reference. Within the analyzed abundance domain, these fluctuations showed no consistent positive accumulation over 1 to 5 weeks. ClonoDynamics provides an experimentally benchmarked framework for distinguishing estimator-induced patterns, replicate-consistent longitudinal variation, and temporal accumulation.

immunology↗

bioRxiv2026

Tissue-adapted NK cells shape pathogenic cDC1 niches in early arthritis

Chronic forms of autoimmune arthritis, including juvenile idiopathic arthritis (JIA), are characterised by persistent synovial inflammation. While adaptive mechanisms are well-studied, the innate networks driving early joint disease remain poorly defined. Here, through unbiased profiling of innate lymphoid cells from the joints of children with JIA at disease onset, we identify activated natural killer (NK) cells as key orchestrators of adaptive immune niches. The selective upregulation of lymphotactin (XCL1) by activated NK cells is accompanied by the synovial enrichment of XCR1+ type 1 conventional dendritic cells (cDC1s), directly correlating with disease severity. In situ, NK cells spatially anchor with recruited cDC1s to assemble discrete, multicellular effector niches alongside T cells. Finally, we demonstrate this NK-cDC1 spatial architecture represents a conserved pathogenic module across adult arthropathies, including rheumatoid arthritis. Our findings establish the XCL1-XCR1 axis as a fundamental innate feature of chronic joint inflammation, defining a targetable mechanism that precedes and promotes downstream adaptive responses.

immunology↗

bioRxiv2024

Anti-capsule human monoclonal antibodies protect against hypervirulent and pandrug-resistant Klebsiella pneumoniae

The silent pandemic caused by antimicrobial resistance (AMR) requires innovative therapeutic approaches. Human monoclonal antibodies (mAbs), which are among the most transformative, safe and effective drugs in oncology and autoimmunity, are rarely used for infectious diseases and not yet used for AMR. Here we applied an antigen-agnostic strategy to isolate extremely potent human mAbs against Klebsiella pneumoniae (Kp) sequence type 147 (ST147), a hypervirulent and pandrug-resistant clonotype which is spreading globally. Isolated mAbs target the bacterial capsule and the O-antigen. Surprisingly, although both capsule- and O-antigen-specific mAbs displayed bactericidal activity in the picomolar range in vitro, only the capsule-specific mAbs were protective against fulminant ST147 bloodstream infection. Protection correlated with in vitro bacterial uptake by macrophages and enchained bacterial growth. Our study describes the only drug able to protect against pandrug-resistant Kp and provides a strategy to isolate mAbs and identify correlates of protection against AMR bacteria.

microbiology↗

bioRxiv2023

Extracellular vesicles released by keratinocytes regulate melanosome maturation, melanocyte dendricity and pigment transfer

Extracellular vesicles (EVs) facilitate the transfer of proteins, lipids and genetic material molecules between cells, and are recognized as an additional mechanism for sustaining intercellular communication. In the epidermis, the communication between melanocytes and keratinocytes is tightly regulated to warrant skin pigmentation. Melanocytes synthetize the melanin pigment in melanosomes that are transported along the dendrites prior to the transfer of melanin pigment to keratinocytes. EVs secreted by keratinocytes modulate pigmentation in melanocytes (Lo Cicero et al., Nat. Comm. 2015). However, whether EVs secreted by keratinocytes contribute to additional processes essential for melanocyte functions remains elusive. Here we show that keratinocyte EVs enhance the ability of melanocytes to generate dendrites, mature melanosomes and their efficient transfer. Further, keratinocyte EVs carrying Rac1 induce important morphological changes, promote dendrite outgrowth, and potentiate melanin transfer to keratinocytes. Hence, in addition to modulate pigmentation, keratinocytes exploit EVs to control melanocyte plasticity and transfer capacity. These data demonstrate that keratinocyte-derived EVs, by regulating melanocyte functions, are major contributors of cutaneous pigmentation and expand our understanding of the mechanism underlying skin pigmentation via a paracrine EV-mediated communication. SIGNIFICANCE STATEMENTOur work uncovers how keratinocyte-derived EVs control melanocyte physiology and functions. By promoting the growth of melanocyte dendrites, maturation, accumulation and peripheral positioning of pigmented melanosomes within the dendrites, and transfer of melanin to keratinocytes, EVs released by keratinocytes control crucial processes in skin photo protection. Importantly, given that dysregulation of these pathways could underlie pigment disorders, melanoma or skin carcinoma, our results open avenues to exploit keratinocyte EVs as tools for the design of new therapies to enhance the ability of melanocytes to provide skin photoprotection, and thus decrease the incidence pigmentary disorders and skin cancers.

cell biology↗

bioRxiv2018

Impact of high phosphorous and sodium on productivity and stress tolerance of Arundo donax plants

Arundo donax L. is an invasive species recently employed for biomass production that emits large amounts of isoprene, a volatile compound having important defensive role. Here, the potential of A. donax to grow in degraded soils, characterized by poor fertility, eutrophication and/or salinization, has been evaluated at morphological, biochemical and transcriptional level. Our results highlight sensitivity of A. donax to P deficiency. Moreover, we show that A. donax response to salt stress (high sodium, Na+), which impaired plant performance causing detrimental effects on leaf cells ultrastructure, is characterized by enhanced biosynthesis of antioxidant carotenoids and sucrose. Differently from Na+, high phosphorous (P) supply did not hamper photosynthesis although it affected carbon metabolism through reduction of starch content and by lowering isoprene emission. In particular, we revealed on salt-stress leaves that high P enhanced the expression of genes involved in abiotic stress tolerance, but further increased diffusive limitations to photosynthesis and slowed-down sugar turnover without modifying isoprene emission. Therefore, despite limiting productivity, high P improved A. donax tolerance to salinity by favouring the accumulation of carbohydrates that protect cells and increase osmotic potential, and by stimulating the synthesis of antioxidants that improves photo-protection and avoids excessive accumulation of reactive oxygen species.\n\nHighlightsArundo donax is sensitive to elevated salinity. High phosphorous supply to salt-stressed A. donax enhances transcriptomic changesthat induce the onset of physiological mechanisms of stress tolerance but limits productivity.

physiology↗