Biology subjects

Bo, L.

Publications and source records attributed to Bo, L..

5 recordsLinked to original sources

bioRxiv2026

Inflammation-induced of Clec18a inhibits immune responses via Trpm7-dependent Cbl activation

Innate immune responses must be tightly controlled to maintain immuno-homeostasis. However, the regulatory mechanisms underlying the activation and early stages of the innate immune response remain poorly defined. Here, we found the soluble C-type lectin Clec18a is up-regulated in multiple inflammatory diseases, including sepsis and influenza, and secreted within minutes upon activation in multiple immune cells, including macrophages, dendritic cells (DCs), and T cells. Clec18a-myeloid-knockout mice exhibited reduced survival and exacerbated inflammation than the wild-type. However, exogenous recombinant Clec18a administration alleviated inflammation both in vitro and in vivo. Mechanistically, we identified macrophage-inducible C-type lectin (Mincle) as the receptor of Clec18a. Clec18a-Mincle binding triggers Trpm7-dependent calcium influx, which activates the ubiquitin E3 ligase Cbl and leads to Mincle-Cbl-MyD88-Trpm7 complex formation and degradation. Cbl deficiency, calcium inhibition and Trpm7 knockdown abrogated Clec18a-mediated immune suppression. Thus, our study revealed Clec18a as a critical checkpoint on the initiation of innate immune response through an intrinsic crosstalk between CLR and TLR signaling.

immunology↗

bioRxiv2026

Marmosets adaptively accumulate dynamic sequential evidence to make decisions

The bounded accumulation model is a dominant theoretical framework to characterize evidence accumulation during decision-making. Using a dynamic sequential tone accumulation (DSTA) task in marmosets, we found that the contribution of late tones to decisions was greater for weaker than for stronger evidence strength-an effect we term evidence-strength-dependent temporal weighting (ETW). Rigorous exclusionary analyses and drift-diffusion modeling further revealed that the bounded accumulation mechanism alone fails to account for this effect, and the online modulation of attentional engagement was identified as the necessary mechanism in addition to the bounded accumulation. Our work thus establishes that attentional engagement is adaptively modulated by evidence strength during complex decision-making.

neuroscience↗

bioRxiv2025

High-dimensional Immune Profiling Following Autologous Hematopoietic Stem Cell Transplantation in Relapsing-Remitting Multiple Sclerosis

Background and ObjectivesAutologous hematopoietic stem cell transplantation (aHSCT) induces durable remission in treatment-refractory relapsing-remitting multiple sclerosis (RRMS). However, to what extent post-transplant immune recovery reflects restoration of pre-treatment state versus selective remodeling remains incompletely understood. We used high-dimensional whole-blood immune profiling to characterize lineage-specific remodeling in patients with RRMS following aHSCT and to compare trajectories with healthy reference profiles. MethodsPeripheral blood from 25 patients with RRMS treated with aHSCT in the RAM-MS trial was analyzed longitudinally at baseline, 100 days, and 6, 12, and 24 months post-transplant. Samples were compared with those from 9 age- and sex-matched healthy controls using a 41-marker mass cytometry panel. Unsupervised clustering and multi-level modeling were used to quantify lineage-level abundance changes and phenotypic remodeling across adaptive and innate compartments. ResultsImmune recovery after aHSCT was characterized by selective and sustained reshaping of specific T-and B-cell subsets rather than uniform restoration of pre-treatment composition. Naive CD4+ and CD8+ T cells gradually repopulated, whereas memory CD4+ T cells remained reduced at 24 months. Memory CD8+ T cells showed a transient early expansion before declining toward baseline levels. Naive B cells expanded early and remained elevated, while memory B cells were durably reduced. B-cell reconstitution involved expansion of activation-associated naive populations alongside contraction of selected memory subsets. Across T-cell compartments, CD161-expressing chemokine receptor-enriched subsets were selectively depleted. Several of these alterations persisted despite partial normalization of overall cell counts. These trajectories were consistent across patients, supporting a robust and reproducible effect of aHSCT on immune architecture. DiscussionaHSCT induces durable, lineage-specific reorganization of adaptive immunity along a shared trajectory across patients, characterized by contraction of inflammatory T-cell programs and hierarchical restructuring of B-cell maturation rather than simple immune restoration.

immunology↗

bioRxiv2021

Identification of age-associated proteins and functional alterations in human primary retinal pigment epithelium cells

BackgroundRetinal pigmented epithelium (RPE) has essential functions to nourish and support the neural retina, and is of vital importance in the pathogenesis of age-related retinal degeneration. However, the exact molecular changes of RPE in aging remain poorly defined. MethodsWe isolated human primary RPE (hRPE) cells from 18 eye donors distributed over a wide age range (10 - 67 years). A quantitative proteomic analysis was performed to analyze their intracellular and secreted protein changes, and potential age-associtated mechanisms were validated by ARPE-19 and hRPE cells. ResultsAge-stage related subtypes and age-associtated proteins and functional alterations were revealed. Proteomic data and verifications showed that RNF123 and RNF149 related ubiquitin-mediated proteolysis might be an important clearance mechanism in elimination of oxidative damaged proteins in aged hRPE. In older hRPE cells, apoptotic signaling related pathways were up-regulated and endoplasmic reticulum organization was down-regulated both in intracellular and secreted proteome. ConclusionsThis work paints a detailed molecular picture of human RPE in aging process and provides new insights for molecular characteristics of RPE in aging and related clinical retinal conditions.

bioinformatics↗

bioRxiv2021

Inferring the stabilization effects of SARS-CoV-2 variants on the binding with ACE2 receptor

With the progression of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, several variants of the virus are emerging with mutations distributed all over the viral sequence. While most of them are expected to have little to no effects at the phenotype level, some of these variants presenting specific mutations on the Spike protein are rapidly spreading, making urgent the need of characterizing their effects on phenotype features like contagiousness and antigenicity. With this aim, we performed extensive molecular dynamics simulations on a selected set of possible Spike variants in order to assess the stabilizing effect of particular amino acid substitutions, with a special focus on the mutations that are both characteristic of the top three most worrying variants at the moment, i.e the English, South African and Amazonian ones, and that occur at the molecular interface between SARS-CoV-2 Spike protein and its human ACE2 receptor. We characterize these variants effect in terms of (i) residues mobility, (ii) compactness, studying the network of interactions at the interface, and (iii) variation of shape complementarity via expanding the molecular surfaces in the Zernike basis. Overall, our analyses highlighted greater stability of the three variant complexes with respect to both the wild type and two negative control systems, especially for the English and Amazonian variants. In addition, in the three variants, we investigate the effects a not-yet observed mutation in position 501 could provoke on complex stability. We found that a phenylalanine mutation behaves similarly to the English variant and may cooperate in further increasing the stability of the South African one, hinting at the need for careful surveillance for the emergence of such kind of mutations in the population. Ultimately, we show that the observables we propose describe key features for the stability of the ACE2-spike complex and can help to monitor further possible spike variants.

biophysics↗