bioRxiv Science⌕ Search

Biology subjects

Lim, H.

Publications and source records attributed to Lim, H..

At least 19 recordsLinked to original sources

Inertial coupling between swing and stance legs shapes ankle torque profile during running

The spring-loaded inverted pendulum (SLIP) model has effectively explained center of mass (CoM) and ground reaction force (GRF) dynamics during human gait despite its simplicity, describing both walking and running within the same mechanical principles. A recent study extended the explanatory capability of the SLIP model to joint dynamics by reproducing ankle joint dynamics during walking. However, during running, the model did not capture the empirical ankle torque profile, suggesting that such mechanical unification may not hold at the joint level. Because the previous model represented the body as a single point mass, it neglected leg inertia, which may become important during running as rapid motion generates substantial angular momentum. To address this limitation, we propose an extended two-mass model that separates the whole-body mass into the swing-leg and the remaining body mass, thereby explicitly incorporating swing-leg inertia into stance-leg joint dynamics. The swing leg is modeled using a linear spring and a torsional spring at the hip joint for its radial and rotational motion. Through inertial coupling, swing-leg dynamics influence the stance-leg ankle torque. Consequently, the proposed model reproduces the symmetric, single-peaked ankle torque profile observed experimentally while preserving the CoM and GRF of the previous model. These findings suggest that the discrepancy of the previous model during running may be explained by the omission of swing-leg inertia. By accounting for the gait-mode-dependent contribution of swing-leg inertia, the proposed model provides a unified mechanical framework for extending simple gait models from CoM-level behavior to joint dynamics.

bioengineering↗

Lower-limb mechanical power accounts for running energy expenditure and enables single-IMU estimation

Energy expenditure (EE) during running depends on the interplay between active muscle work and elastic energy storage and return, yet the relative contribution of mechanical power to EE remains debated. Quantifying the relative contributions of segment-level mechanical power can provide a way to address this debate. In this study, we aimed to quantify how segment-level mechanical power contributes to EE during running and to demonstrate that these mechanistic insights support wearable-based EE estimation. Joint dynamics and respiratory gas-based EE were collected from healthy young adults running at multiple speeds. Scale factors were derived to quantitatively link efficiency-weighted segment power to measured EE. The stance leg consistently showed the strongest correlation with EE, and this dominance was preserved across speeds. Including swing-leg hip power further improved accuracy. Scale factors were approximately 0.45, suggesting that active muscle work and elastic energy return contribute comparably to the mechanical power associated with EE. Using a lightweight machine learning model, stance-leg and swing-leg hip joint power were reconstructed from a single sacral IMU, enabling accurate EE prediction. These findings demonstrate that lower-limb mechanical power is a robust predictor of running EE, supporting both the extensibility of biomechanically-informed frameworks and wearable-based EE monitoring.

bioengineering↗

A transcriptional code controlling fluid shear stress-induced gene expression

The formation and health of the vascular system is dependent on fluid shear stress (FSS), a hemodynamic force exerted onto endothelium by flowing blood. FSS strongly induces the endothelial expression of Kruppel-like factor 2 (KLF2), an atheroprotective TF essential for vascular development and homeostasis. Despite its early and crucial role in the cascade of cardiovascular events triggered by FSS, the transcriptional mechanisms by which FSS regulates KLF2 expression remain unclear, although they are known to involve the widely expressed MEF2 proteins. Here, we identified and characterized two FSS-dependent enhancers for KLF2 which collectively recapitulate endogenous endothelial KLF2 expression, and determined the TFs contributing to their regulation. This analysis identified an essential and precisely spaced MEF2-TBP double motif also shared by the FSS-sensitive KLF2 promoter. MEF-TBP double motifs are extremely rare across the genome but were also found within regulatory elements of three other FSS-induced KLF genes, including KLF4. Although normally part of the basal transcriptional machinery, TBP specifically bound all KLF elements at the MEF-TBP double motifs in a FSS-dependent manner. Collectively, this work demonstrates a specific and targetable requirement for combined MEF2-TBP binding during FSS-induced gene activation. Significance statementBlood flow induces a force known as fluid shear stress (FSS) which is required for vascular development and for the health of the mature arterial system. One of the first endothelial responses to FSS is the induction of Kruppel-like transcription factors (KLFs). However, the mechanisms by which FSS activates KLF gene expression are incompletely understood. In this paper, we characterized all regulatory elements involved in driving FSS-induced expression of KLF2. This identified an essential MEF2-TBP double motif that was extremely rare across the genome, yet found within regulatory elements for multiple FSS-responsive KLF genes including KLF2 and KLF4. This MEF2- and TBP-bound motif therefore enables blood flow to specifically activate the cascade of cardiovascular responses necessary for atheroprotective gene expression.

developmental biology↗

Amplified MS2 labeling reveals heterogeneous dynamics of RNA granules in the live murine brain

Dynamics of messenger ribonucleic acids (mRNAs) and the complexes with associated proteins (RNPs), also known as RNA granules, provide post-transcriptional control of gene expression. This regulation is crucial for cell-type diversity and activity-dependent plasticity of the mammalian central nervous system (CNS). However, elucidating the physiological significance of RNA granules has been hampered by the lack of technologies for probing them in live mouse brain. Here, we describe a novel method to visualize RNA granules in native CNS tissues in vivo. To amplify the fluorescence signal from single mRNAs incorporating MS2 stem loops, MS2 capsid protein (MCP) was conjugated with 4 tandem superfolder green fluorescent proteins (sfGFPs). Using MCP-4xsfGFP, a significant population of RNPs could be detected in specific cells of the CNS, enabling new findings, e.g., remarkable heterogeneity of Actb mRNA dynamics across neurons and glial cells. The highly sensitive in vivo RNA imaging could be useful for illuminating the regulation of the dynamics of RNA granules in naive and diseased animals. SignificanceRNA granules, complexes of RNAs and binding proteins, play a vital role in regulating gene expression and mRNA dynamics. Despite the importance, monitoring their behavior in functional neural tissue has proven technically challenging, in part due to optical turbidity and weak fluorescent tags. In this study, we present a new approach to better observe RNA granules in specific cells of murine brain through the use of amplified fluorescent signals and advanced imaging techniques. Our method provides a powerful means to analyze the properties of RNA granules within neurons and glial cells in vivo, offering valuable insights into healthy and neurodegenerative brains.

neuroscience↗

Evolution guided tolerance engineering of Pseudomonas putida KT2440 for production of the sustainable aviation fuel precursor isoprenol

Isoprenol (3-methyl-3-buten-1-ol) is a sustainable aviation fuel precursor and commodity chemical which can be microbially synthesized from renewable carbon streams. Its production has been demonstrated in Pseudomonas putida KT2440 but its titers, rates, and yields have yet to reach commercially viable levels, potentially due to its inherent toxicity. We hypothesized that utilization of Tolerization Adaptive Laboratory Evolution (TALE) would generate P. putida hosts more tolerant to isoprenol and suitable for enhanced production phenotypes. Here, we performed a comprehensive TALE campaign using three strains, the wild-type and two strains lacking subsets of known isoprenol catabolism and transport functions in quadruplicate independently evolved lineages. Several evolved clones from each starting strain displayed robust growth (up to 0.2 h-1) at 8 g/L of isoprenol, where starting strains could not grow. Whole genome resequencing of the 12 independent strain lineages identified convergent mutations. Reverse engineering four commonly mutated regions individually (gnuR, ttgB-PP_1394, PP_3024-PP_5558, PP_1695) each resulted in a partial recovery of the tolerance phenotypes observed in the evolved strains. Additionally, a proteomics-guided deletion of the master motility regulator, fleQ, in an evolved clone alleviated the tolerance vs. production trade-off, restoring isoprenol titers and consumption to levels observed in the starting strains. Collectively, this work demonstrated that an integrated strategy of laboratory evolution and rational engineering was effective to develop robust biofuel production hosts with minimized product toxicity.

microbiology↗

Optogenetic control of Protein Kinase C-epsilon activity reveals its intrinsic signaling properties with spatiotemporal resolution

The regulation of PKC epsilon (PKC{varepsilon}) and its downstream effects is still not fully understood, making it challenging to develop targeted therapies or interventions. A more precise tool that enables spatiotemporal control of PKC{varepsilon} activity is thus required. Here, we describe a photo-activatable optogenetic PKC{varepsilon} probe (Opto-PKC{varepsilon}) consisting of an engineered PKC{varepsilon} catalytic domain and a blue-light inducible dimerization domain. Molecular dynamics and AlphaFold simulations enable rationalization of the dark-light activity of the optogenetic probe. We first characterize the binding partners of Opto-PKC{varepsilon}, which are similar to those of PKC{varepsilon}. Subsequent validation of the Opto-PKC{varepsilon} tool is performed with phosphoproteome analysis, which reveals that only PKC{varepsilon} substrates are phosphorylated upon light activation. Opto-PKC{varepsilon} could be engineered for recruitment to specific subcellular locations. Activation of Opto-PKC{varepsilon} in isolated hepatocytes reveals its sustained activation at the plasma membrane is required for its phosphorylation of the insulin receptor at Thr1160. In addition, Opto-PKC{varepsilon} recruitment to the mitochondria results in its lowering of the spare respiratory capacity through phosphorylation of complex I NDUFS4. These results demonstrate that Opto-PKC{varepsilon} may have broad applications for the studies of PKC{varepsilon} signaling with high specificity and spatiotemporal resolution. SummaryWe have developed a photo-activatable optogenetic PKC{varepsilon} probe, which demonstrates differential activity in light versus dark. The tool is subsequently validated with protein association studies and phosphoproteome analysis. It enables dissection of signaling events arising from its activation at defined subcellular locations. For instance, sustained activation of PKC{varepsilon} at the plasma membrane is required for its phosphorylation of the insulin receptor at Thr1160.

molecular biology↗

Correcting errors in PCR-derived libraries for rare allele detection by reconstructing parental and daughter strand information

Molecular barcoding methods enable high-sensitivity detection of circulating tumor DNA that is rarely present in liquid biopsy samples. Many methods involve ligation of molecular barcodes to DNA prior to hybridization capture, enabling recovery of starting molecules. Development of polymerase chain reaction (PCR)-based methods could facilitate more cost- and labor- effective detection; however, tracking molecular identity can be difficult, as new barcodes overwrite old barcodes in each cycle. We developed a sensitive genotyping method based on a peer-to-peer network-derived identifier for error reduction in amplicon sequencing (SPIDER-seq) and enable molecular identity tracking with PCR-derived libraries using overwritten barcodes. SPIDER-seq detected mutations at frequences as low as 0.125% after only two consecutive general PCR cycles and systematically analyzed the error pattern in the peer-to-peer network. Our method could facilitate the rapid detection of mutations associated with various cancers.

bioinformatics↗

IOP-induced blood-retinal barrier compromise contributes to RGC death in glaucoma

The integrity of the blood-retinal barrier (BRB) has been largely unexplored in glaucoma. We reveal that elevated intraocular pressure (IOP) partially compromises the BRB in two human-relevant inherited mouse models of glaucoma (DBA/2J and Lmx1bV265D). Experimentally increasing IOP in mouse eyes further confirms this. Notably, the compromise induces subtle leakage, happening without bleeding or detected endothelial cell junction disruption, and it precedes neurodegeneration. Leakage occurs from peripheral veins in the retinal ganglion cell layer with a concomitant loss of the transcytosis inhibitor MFSD2A. Importantly, stabilizing {beta}-catenin in retinal endothelial cells prevents both vascular leakage and neurodegeneration in the DBA/2J model. The occurrence of leakage in all 3 high IOP models indicates that BRB compromise may be a common, yet overlooked, mechanism in glaucoma. These findings suggest that IOP-induced BRB compromise plays a critical role in glaucoma, offering a new therapeutic target.

neuroscience↗

TLR4 deficiency does not alter glaucomatous progression in a mouse model of chronic glaucoma

Glaucoma is a leading cause of irreversible blindness worldwide. Toll-like receptor 4 (TLR4) is a pattern-recognition transmembrane receptor that induces neuroinflammatory processes in response to injury. Tlr4 is highly expressed in ocular tissues and is known to modulate inflammatory processes in both anterior and posterior segment tissues. TLR4 activation can lead to mitochondrial dysfunction and metabolic deficits in inflammatory disorders. Due to its effects on inflammation and metabolism, TLR4 is a candidate to participate in glaucoma pathogenesis. It has been suggested as a therapeutic target based on studies using acute models, such as experimentally raising IOP to ischemia-inducing levels. Nevertheless, its role in chronic glaucoma needs further evaluation. In the current study, we investigated the role of TLR4 in an inherited mouse model of chronic glaucoma, DBA/2J. To do this, we analyzed the effect of Tlr4 knockout (Tlr4-/-) on glaucoma-associated phenotypes in DBA/2J mice. Our studies found no significant differences in intraocular pressure, iris disease, or glaucomatous progression in Tlr4-/- compared to Tlr4+/+ DBA/2J mice. These data do not identify a role for TLR4 in this chronic glaucoma, but further research is warranted to understand its role in other glaucoma models and different genetic contexts.

neuroscience↗

The Chemokine Receptor CCR8 is Not a High-affinity Receptor for the Human Chemokine CCL18

The primate-specific chemokine CCL18 is a potent chemoattractant for T cells and is expressed at elevated levels in several inflammatory diseases. However, the cognate receptor for CCL18 remains unconfirmed. Here, we describe attempts to validate a previous report that the chemokine receptor CCR8 is the human CCL18 receptor (Islam et al. J Exp Med. 2013, 210:1889-98). Two mouse pre-B cell lines (4DE4 and L1.2) exogenously expressing CCR8 exhibited robust migration in response to the known CCR8 ligand CCL1 but not to CCL18. Similarly, CCL1 but not CCL18 induced internalization of CCR8 on 4DE4 cells. CCR8 expressed on Chinese hamster ovarian (CHO) cells mediated robust G protein activation, inhibition of cAMP synthesis and {beta}-arrestin2 recruitment in response to CCL1 but not CCL18. Several N- and C-terminal variants of CCL18 also failed to stimulate CCR8 activation. On the other hand, and as previously reported, CCL18 inhibited CCL11-stimulated migration of 4DE4 cells expressing the receptor CCR3. These data suggest that CCR8, at least in the absence of unidentified cofactors, does not function as a high affinity receptor for CCL18.

immunology↗

Morphology, but not microtubules, of the retinal nerve fibers are protected by nicotinamide in glaucoma mice

Glaucoma is a blinding disease where the retinal ganglion cells and their axons degenerate. Degradation of axonal microtubules is thought to play a critical role in the pathogenesis, but the mechanism is unknown. Here we investigate whether microtubule disruption in glaucoma can be alleviated by metabolic rescue. The morphology and integrity of microtubules of the retinal nerve fibers were evaluated by second-harmonic generation microscopy in a mouse model of glaucoma, DBA/2, which received a dietary supplement of nicotinamide to reduce metabolic stress. It was compared with control DBA/2, which did not receive nicotinamide, and non-glaucomatous DBA/2-Gpnmb+. We found that morphology but not microtubules are significantly protected by nicotinamide. Furthermore, from co-registered images of second-harmonic generation and immunofluorescence, it was determined that microtubule deficit was not due to a shortage of tubulins. Microtubule deficit colocalized with the sectors in which the retinal ganglion cells were disconnected from the brain, indicating that microtubule disruption is associated with axonal transport deficit in glaucoma. Together, our data suggests significant role axonal microtubules play in glaucomatous degeneration, offering a new opportunity for neuroprotection.

neuroscience↗

Epithelial N-methyl-D-aspartate (NMDA) receptors mediate renal vasodilation by affecting kidney autoregulation.

BackgroundN-methyl-D-aspartate receptor (NMDAR) are amino acid receptors that are well studied in brain physiology; however, their role in kidney is poorly understood. Nonetheless, NMDAR inhibitors can increase serum K+ and reduce GFR, which suggests they have an important physiological role in the kidney. We hypothesized that NMDARs in the distal nephron induce afferent-arteriole vasodilation through the vasodilator mechanism connecting-tubule-glomerular feedback (CNTGF) that involves ENaC activation. Methods and resultsUsing a tubule-specific transcriptome database combined with molecular biology and microscopy techniques, we showed kidney expression of NMDAR subunits along the nephron and specifically in ENaC-positive cells. This receptor is expressed in both male and female mice, with higher abundance in females (p=0.02). Microperfusing NMDAR agonists into the connecting tubule induced afferent-arteriole vasodilation (EC50 10.7 vs. 24.5 mM; p<0.001) that was blunted or eliminated with the use of NMDAR blocker MK-801 or with the ENaC inhibitor Benzamil, indicating a dependence on CNTGF of the NMDAR-induced vasodilation. In vivo, we confirmed this CNTGF-associated vasodilation using kidney micropuncture (Stop-flow pressure 37.9{+/-}2.6 vs. 28.6{+/-}1.9 mmHg, NMDAR agonist vs vehicle; p<0.01). We explored NMDAR and ENaC channel interaction by using mpkCCD cells and split-open connecting tubules. We observed increased amiloride-sensitive current following NMDAR activation that was prevented by MK-801 (1.14 vs. 0.4 Amp; p=0.03). In split-open tubules, NMDAR activation increased ENaC activity (Npo Vehicle vs. NMDA; p=0.04). ConclusionNMDARs are expressed along the nephron, including ENaC-positive cells, with higher expression in females. Epithelial NMDAR mediates renal vasodilation through the connecting-tubule-glomerular feedback, by increasing ENaC activity.

physiology↗

An eco-physiological model of forest photosynthesis and transpiration under combined nitrogen and water limitation

Although the separate effects of water and nitrogen (N) limitations on forest growth are well known, the question of how to predict their combined effects remains a challenge for modeling of climate change impacts on forests. Here, we address this challenge by developing a new eco-physiological model that accounts for plasticity in stomatal conductance and leaf N concentration. Based on an optimality principle, our model determines stomatal conductance and leaf N concentration by balancing carbon uptake maximization, hydraulic risk and cost of maintaining photosynthetic capacity. We demonstrate the accuracy of the model predictions by comparing them against gross primary production estimates from eddy covariance flux measurements and sap-flow scaled canopy transpiration in a long-term fertilized and an unfertilized Scots pine (Pinus sylvestris L.) forest in northern Sweden. The model also explains the response to N fertilization as a consequence of (i) reduced carbon cost of N uptake and (ii) increased leaf area per hydraulic conductance. The results suggest that leaves optimally coordinate N concentration and stomatal conductance both on short (weekly) time scales in response to weather conditions and on longer time scales in response to soil water and N availabilities.

ecology↗

Generalizing deep variant callers via domain adaptation and semi-supervised learning

Deep learning-based variant callers (DVCs) offer state-of-the-art perfor-mance in small variant detection from DNA sequencing data. However, their reliance on supervised learning and the subsequent need for exten-sive labeled data pose a potential hurdle to their generalizability across diverse sequencing methods with varying error profiles. Indeed, even minor discrepancies in error profiles can compromise the robustness of DVCs and impair the variant calling accuracy in the target sequencing method. To mitigate these challenges, we propose RUN-DVC, the first semi-supervised training approach for DVCs that presents two complemen-tary training techniques to the conventional supervised training approach. RUN-DVC leverages semi-supervised learning techniques to learn error profiles from unlabeled datasets of the target sequencing method as well as a domain adaptation technique to aid semi-supervised learning by reducing the domain discrepancy due to different error profiles. We ana-lyze and contrast RUN-DVC against the supervised training approach under various generalization scenarios using nine sequencing methods from Illumina, BGI, PacBio, and Oxford Nanopore sequencing platforms. Remarkably, RUN-DVC significantly improves the variant calling accu-racy of DVC in the target sequencing method even with purely unlabeled datasets in the target domain and enables label-efficient generalization when partially labeled datasets are available. Our results suggest RUN-DVC is a promising semi-supervised training method for DVCs with the potential to broaden the use of DVC across diverse sequencing methods.

bioinformatics↗

A developmentally-inspired hypoxia condition promotes kidney organoid differentiation from human pluripotent stem cells

Kidney organoids derived from human pluripotent stem cells (hPSCs) lack a contiguous network of collecting ducts, which limits their utility in modeling kidney development and disease. Here, we report the generation of kidney organoids containing ureteric bud (UB)-derived collecting ducts connected to metanephric mesenchyme (MM)-derived nephrons using developmentally-inspired hypoxic differentiation conditions. Hypoxia promotes a reiterative process of branching morphogenesis and nephron induction through reciprocal interactions between co-induced MM and UB, which lead to a higher-order kidney organogenesis in vitro. The resulting kidney organoids demonstrate greater maturity, as indicated by higher levels of functional markers and more realistic micro-anatomy of the tubules and collecting ducts. Additionally, these hypoxic-enhanced kidney organoids show a great potential as in vitro models for renal cystic diseases, as they efficiently generate cystic formations and display high sensitivity to drugs. This hypoxia approach may open new avenues for an enhanced understanding of kidney development and diseases.

bioengineering↗

Elastic fibers define embryonic tissue stiffness to enable buckling morphogenesis of the small intestine

During embryonic development, tissues must possess precise material properties to ensure that cell-generated forces give rise to the stereotyped morphologies of developing organs. However, the question of how material properties are established and regulated during development remains understudied. Here, we aim to address these broader questions through the study of intestinal looping, a process by which the initially straight intestinal tube buckles into loops, permitting ordered packing within the body cavity. Looping results from elongation of the tube against the constraint of an attached tissue, the dorsal mesentery, which is elastically stretched by the elongating tube to nearly triple its length. This elastic energy storage allows the mesentery to provide stable compressive forces that ultimately buckle the tube into loops. Beginning with a transcriptomic analysis of the mesentery, we identified widespread upregulation of extracellular matrix related genes during looping, including genes related to elastic fiber deposition. Combining molecular and mechanical analyses, we conclude that elastin confers tensile stiffness to the mesentery, enabling its mechanical role in organizing the developing small intestine. These results shed light on the role of elastin as a driver of morphogenesis that extends beyond its more established role in resisting cyclic deformation in adult tissues.

developmental biology↗

CyuR is a Dual Regulator for L-Cysteine Dependent Antimicrobial Resistance in Escherichia coli

Hydrogen sulfide (H2S), mainly produced from L-cysteine (Cys), renders bacteria highly resistant to oxidative stress. This mitigation of oxidative stress was suggested to be an important survival mechanism to achieve antimicrobial resistance (AMR) in many pathogenic bacteria. CyuR (known as DecR or YbaO) is a recently characterized Cys-dependent transcription regulator, responsible for the activation of the cyuAP operon and generation of hydrogen sulfide from Cys. Despite its potential importance, the regulatory network of CyuR remains poorly understood. In this study, we investigated the roles of the CyuR regulon in a Cys-dependent AMR mechanism in E. coli strains. We found: 1) Cys metabolism has a significant role in AMR and its effect is conserved in many E. coli strains, including clinical isolates; 2) CyuR negatively controls the expression of mdlAB encoding a transporter that exports antibiotics such as cefazolin and vancomycin; 3) CyuR binds to a DNA sequence motif GAAwAAATTGTxGxxATTTsyCC in the absence of Cys, confirmed by an in vitro binding assay; and 4) CyuR may regulate 25 additional genes as suggested by in silico motif scanning and transcriptome sequencing. Collectively, our findings expanded the understanding of the biological roles of CyuR relevant to antibiotic resistance associated with Cys.

systems biology↗

Mass cytometry identifies dysregulation of circulating and cutaneous immune cells in patients with hidradenitis suppurativa

2.BackgroundHidradenitis suppurativa (HS) is a multifactorial, inflammatory skin disease. Increased systemic inflammatory comorbidities and serum cytokines highlight systemic inflammation as a feature of HS. However, the specific immune cell subsets contributing to systemic and cutaneous inflammation have not been resolved. ObjectiveIdentify features of peripheral and cutaneous immune dysregulation. MethodsHere, we generated whole-blood immunomes by mass cytometry. We performed a meta-analysis of RNA-seq data, immunohistochemistry, and imaging mass cytometry to characterize the immunological landscape of skin lesions and perilesions from patients with HS. ResultsBlood from patients with HS exhibited lower frequencies of natural killer cells, dendritic cells, and classical (CD14+CD16-) and nonclassical (CD14-CD16+) monocytes, as well as higher frequencies of Th17 cells and intermediate (CD14+CD16+) monocytes than blood from healthy controls. Classical and intermediate monocytes from patients with HS had increased expression of skin-homing chemokine receptors. Furthermore, we identified a CD38+ intermediate monocyte subpopulation that was more abundant in the immunome of blood from patients with HS. Meta-analysis of RNA-seq data found higher CD38 expression in lesional HS skin than in perilesional skin, and markers of classical monocyte infiltration. Imaging mass cytometry showed that CD38+ classical monocytes and CD38+ monocyte-derived macrophages were more abundant in lesional HS skin. ConclusionOverall, we report targeting CD38 may be worth pursuing in clinical trials. 3. Key MessagesO_LIMonocyte subsets express markers of activation in circulation and HS lesions C_LIO_LITargeting CD38 may be a viable strategy for treating systemic and cutaneous inflammation in patients with HS C_LI 4. Capsule SummaryDysregulated immune cells in patients with HS express CD38 and may be targeting by anti-CD38 immunotherapy.

immunology↗