Function (Oxford, England)最新文献

{"title":"An \"old\" cytokine's new trick: IL-1β in B cells and the germinal center.","authors":"Juliana Restrepo Munera, Elise M Rizzi, S Rameeza Allie","doi":"10.1152/function.105.2025","DOIUrl":"10.1152/function.105.2025","url":null,"abstract":"<p><p>IL-1β is typically associated with the innate response, often produced following the detection of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). It is also identified as a cytokine involved in bridging the innate and adaptive immune responses, in which innate cells, like dendritic cells, use IL-1β to activate T cells for the adaptive immune response. The role of IL-1 signaling has been established in the context of T cell differentiation and function, particularly in its regulation of T follicular helper (TFH) cells. Recent work has demonstrated that with TFH function primarily acting within the germinal center (GC), a local source of IL-1β must be present, identifying GC B cells as a critical source of IL-1β. Here we discuss the roles of cells within the GC milieu, the cytokines they produce, and their impact on the GC. In addition, we also discuss the findings from studies examining the molecular mechanisms underlying IL-1β production in B cells and its impact on B cell function. This review is especially relevant as it draws together findings from various disease pathologies to consolidate our current understanding of B cell subsets producing IL-1β and IL-1β signaling within the GC, in both T cells and B cells.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e1052025"},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13218625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role for endothelin-1 in cardiometabolic dysfunction with intermittent hypoxia.","authors":"Anna M Gonsalves, Sarah E Baker, Prachi Singh, Jacqueline K Limberg","doi":"10.1152/function.014.2026","DOIUrl":"10.1152/function.014.2026","url":null,"abstract":"<p><p>Endothelin-1 (ET-1) has been linked to increased hypoxic sensitivity of the chemoreceptors and the development of cardiometabolic disease. Repeated hypoxic exposures [i.e., intermittent hypoxia (IH)] elicit increases in ET-1, muscle sympathetic nerve activity (MSNA), and blood pressure (BP). In this brief review, we summarize data from our group(s) which examined the effect of acute IH on MSNA, BP, and indices of adipose tissue lipolysis [i.e., free fatty acids (FFAs)], as well as the role of ET-1 in these responses. Herein, we show that acute ET receptor inhibition (oral bosentan) attenuates the rise in BP during hypoxia and the fall in BP during hyperoxia in healthy young men. Although the effect of IH on MSNA and BP was not attenuated following ET-receptor inhibition, IH increased plasma ET-1, epinephrine, and FFA concentrations. Notably, inhibition of ET-1 receptors with oral bosentan attenuated the IH-mediated rise in epinephrine and FFA. With these findings, we demonstrate a role for ET-1 in the maintenance of resting BP in young men, possibly through a chemoreceptor-mediated mechanism. We further speculate that the effect of ET-1 receptor inhibition on circulating FFA is secondary to its ability to reduce sympathoadrenal tone during IH exposure. Results highlighted in this review may serve as the basis for future work exploring ET-1 as a therapeutic target for cardiometabolic dysfunction associated with IH.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e0142026"},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13245879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147965760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aberrant activation of renal functional reserve and reduced tubule flow, but not obstruction, is associated with cystogenesis in <i>Pkd2</i> mutant kidneys.","authors":"Isis N Thomas, Sneha Rajendran, Zhang Li, Courtney J Haycraft, Mandy J Croyle, Bradley K Yoder","doi":"10.1152/function.114.2025","DOIUrl":"10.1152/function.114.2025","url":null,"abstract":"<p><p>Disruption of PKD2 function causes polycystic kidney disease (PKD) and leads to the formation of cysts in the kidney in both mice and humans. PKD is progressive, initiating with the formation of tubule dilations that expand into large cysts, causing the destruction of renal parenchyma and loss of kidney function. The mechanisms initiating tubule dilation and expansion are uncertain. Tubule obstruction has been proposed as a factor contributing to cystogenesis. Here, we utilize a proximal tubule fluorescent dextran uptake assay to evaluate changes in tubule flow that occur during cyst initiation or expansion and functional decline. We did not observe overt signs of tubule obstruction during cyst initiation or expansion, even in larger cysts; however, the rate of tubule flow within individual nephrons was greatly diminished in cystic kidneys. Surprisingly, along with reduced tubule flow rate, we observe an increase in newly labeled dextran cells associated with disease in the <i>Pkd2</i> mutants. These cells are spatially distinct from those absorbing the initial dextran and are detected in both cortical and medullary regions of mutant kidneys. Marker analysis indicated that the dextran⁺ medullary cells were in the loop of Henle and interstitial macrophages. These cells are not present in wild-type controls. This may be due to tubule or vasculature leakage and utilization of renal reserve capacity in mutants that become exhausted, associated with declining glomerular filtration rate (GFR) as cysts expand.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e1142025"},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13307687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148007636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic ketogenesis is not required for exercise training to mitigate diet-induced liver steatosis in male mice.","authors":"Cha Mee Vang, Andres F Ortega, Ruth E Pfeiffer, Jared L Hartmann, Griffin S Hampton, Hu Wang, Eric D Queathem, Peter A Crawford, Xianlin Han, Curtis C Hughey","doi":"10.1152/function.008.2026","DOIUrl":"10.1152/function.008.2026","url":null,"abstract":"<p><p>Accelerated hepatic fatty acid oxidation during acute exercise has been proposed as a contributor to the antisteatotic effects of exercise training. Ketogenesis, which produces acetoacetate (AcAc) and β-hydroxybutyrate (βOHB) from fatty acids, is stimulated by exercise and supports fat oxidation. This study tested the hypothesis that hepatic ketogenesis is necessary for exercise training to lower liver lipids. Liver-specific 3-hydroxymethylglutaryl-CoA synthase 2 knockout (HMGCS2 KO) mice and wild-type (WT) littermates underwent sedentary, acute exercise (treadmill running), and exercise training (6-wk treadmill running regime) protocols. Liver ketone bodies and lipids were determined via mass spectrometry. Stable isotope infusions in conscious, unrestrained mice defined mitochondrial oxidative fluxes during rest and treadmill running. In untrained mice, hepatic HMGCS2 deletion lowered liver AcAc and βOHB and impaired their increase during acute exercise. Liver triacylglycerides (TAGs) were comparable between genotypes at rest (ad libitum fed and short-fasted conditions). In contrast, liver TAGs were higher in HMGCS2 KO compared with WT mice following acute, nonexhaustive exercise. Acute exercise stimulated TCA cycle flux in both genotypes; however, liver TCA cycle flux was higher in KO mice during rest and acute exercise. This suggests that enhanced lipid oxidation via the TCA cycle may be sufficient for TAG homeostasis in HMGCS2 KO mice at rest, but not during acute exercise. Exercise training decreased liver TAGs similarly in WT and KO mice when assessed under short-fasted conditions. In conclusion, hepatic ketogenesis supports liver lipid homeostasis during acute exercise, but is not required for exercise training to mitigate diet-induced fatty liver.<b>NEW & NOTEWORTHY</b> Exercise training has been proposed to mitigate liver steatosis partly through enhanced hepatic fat oxidation. During acute exercise, the oxidation of fatty acids to ketone bodies is stimulated. This study tested the hypothesis that hepatic ketogenesis was required for exercise training to reduce liver fat in mice. The results show that hepatic ketogenesis supports lipid homeostasis during acute exercise, but is not necessary for exercise training to mitigate diet-induced fatty liver.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e0082026"},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147943900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated application of passive mechanical stress produces selective metabolic and extracellular matrix adaptations in human skeletal muscle but does not prevent disuse-induced atrophy.","authors":"Mohadeseh Ahmadi, Charles Seaman, Erik D Marchant, James Bartling, David Kofoed, Karisa Coombs, Chad R Hancock, Robert D Hyldahl","doi":"10.1152/function.109.2025","DOIUrl":"10.1152/function.109.2025","url":null,"abstract":"<p><p>Exposure to mechanical stimuli can modulate skeletal muscle structure and metabolism, yet the extent to which repeated, isolated mechanical stress promotes adaptive remodeling in humans has not been defined. We investigated whether repeated percussive massage (PM)-a widely used but poorly validated therapeutic modality-induces beneficial skeletal muscle adaptations under ambulatory conditions and whether such adaptations confer resilience during limb disuse in humans. In a 6-wk randomized trial, PM did not alter myofiber cross-sectional area, satellite cell abundance, or capillary density, but RNA-Seq pathway analysis revealed enrichment of extracellular matrix (ECM) remodeling networks, which was supported by increases in the expression of basement membrane and focal adhesion components. PM also reduced subcutaneous fat thickness and increased fatty acid-supported mitochondrial respiration while lowering mitochondrial H₂O₂ emission. In a separate 10-day immobilization study, PM failed to attenuate unloading-induced reductions in muscle size or strength. However, PM partially preserved fatty acid-supported respiratory capacity relative to a control group, indicating a selective metabolic resilience. Finally, in an acute mechanistic experiment, unilateral PM did not increase subcutaneous adipose tissue lipolysis, as interstitial glycerol concentrations rose similarly in treated and untreated limbs, suggesting that chronic reductions in subcutaneous fat thickness were not driven by lipolytic activation. Collectively, these findings demonstrate that repeated PM promotes targeted skeletal muscle metabolic adaptations, yet is insufficient to induce overt structural remodeling or prevent disuse-induced functional decline.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e1092025"},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13218624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial CD44 cleavage by ADAM17 impairs shear stress mechanotransduction.","authors":"Gavin Power, Min Jeong Cho, Jesus H Beltran-Ornelas, Marc A Augenreich, Natnicha Imkaew, Olubodun M Lateef, Francisco I Ramirez-Perez, Larissa Ferreira-Santos, Camila Manrique-Acevedo, Luis A Martinez-Lemus, Jaume Padilla","doi":"10.1152/function.113.2025","DOIUrl":"10.1152/function.113.2025","url":null,"abstract":"<p><p>In individuals with type 2 diabetes (T2D), blood flow-mediated increases in endothelial shear stress fail to elicit a robust vasodilatory response. This defective flow-mediated dilation (FMD) is associated with loss of the endothelial glycocalyx, a mechanosensitive extracellular structure that lines the luminal side of blood vessels. Hyaluronan (HA), a polysaccharide constituent of the glycocalyx, is anchored to the plasma membrane by its primary cell-surface receptor, CD44, which is implicated in mechanotransduction of shear stress. Critically, CD44 is also a substrate of a disintegrin and metalloproteinase 17 (ADAM17), a sheddase that is elevated in T2D. However, it is currently unknown whether elevated ADAM17 activity enhances CD44 cleavage from the endothelium and whether this contributes to impaired mechanotransduction and reduced FMD in T2D. Herein, we report elevated plasma HA and ADAM17 activity in a cohort of women and men with T2D and impaired FMD. Moreover, reduced endothelial CD44 is coupled with impaired FMD in arteries isolated from diabetic (<i>db/db)</i> mice. We also provide support for CD44 as a mechanotransducer of HA-associated shear stress mechanosensation and ADAM17-mediated cleavage of CD44 attenuating shear stress mechanotransduction. Finally, using an in-vitro assay and surface plasmon resonance, we show that active recombinant human ADAM17 (ADAM17-r) cleaves recombinant human CD44 and that intraluminal incubation of isolated arteries with ADAM17-r reduces FMD. Collectively, this work supports the role of ADAM17-mediated cleavage of CD44 in impairing endothelial shear stress mechanotransduction.<b>NEW & NOTEWORTHY</b> Impaired flow-mediated dilation (FMD) is an indicator of endothelial dysfunction in type 2 diabetes (T2D). However, the exact cellular and molecular mechanisms contributing to impaired mechanotransduction of shear stress in T2D are incompletely understood. This work supports the novel concept that increased endothelial activity of a disintegrin and metalloproteinase 17 (ADAM17) causes cleavage of cell-surface CD44, leading to loss of hyaluronan (HA)-associated shear stress mechanotransduction.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e1132025"},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147505603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic ketogenic insufficiency blunts exercise-induced energy expenditure and alters mitochondrial proteins in skeletal muscle.","authors":"Xin C Davis, Colin S McCoin, Sebastian F Salathe, Edziu Franczak, Julie A Allen, Eric D Queathem, Kyle L Fulghum, Patrycja Puchalska, Peter A Crawford, John P Thyfault, E Matthew Morris","doi":"10.1152/function.089.2025","DOIUrl":"10.1152/function.089.2025","url":null,"abstract":"<p><p>Ketone body (KB) utilization increases during fasting and exercise due to enhanced hepatic fatty acid oxidation and KB production via the rate-limiting mitochondrial enzyme hydroxymethylglutaryl-CoA synthase (HMGCS2). Since KB metabolism intersects with multiple metabolic pathways and skeletal muscle KB catabolism rises during exercise, we tested the hypothesis that liver-specific HMGCS2 knockouts (KO) would have reduced energy expenditure (EE) and changes in the mitochondrial proteome of skeletal muscle with chronic exercise through voluntary wheel running (VWR), time-restricted feeding (TRF), or both combined to boost hepatic KB production and utilization. Control (CON) and HMGCS2 knockout (KO) mice (<i>n</i> = 6-8 per group) underwent sedentary ad libitum feeding (SED + AL), SED + TRF, VWR + AL, and VWR + TRF for 16 wk, with whole body EE measured using indirect calorimetry. In CON mice, VWR increased total EE by 19.5% and nonresting EE by 50% under AL conditions, and total EE by 16% and nonresting EE by 47.9% under TRF conditions. However, the EE increases seen with VWR did not occur in KO mice. Proteomic analysis revealed that the loss of liver HMGCS2 significantly impacted proteins involved in metabolic processes within skeletal muscle, including reduced oxidative phosphorylation (OXPHOS) protein expression in SED KO mice compared with sedentary CON. Notably, VWR restored OXPHOS protein expression in the muscle of the liver HMGCS2 KO but did not alter it in the CON. Furthermore, muscle from liver HMGCS2 KO mice had elevated expression of glycolytic pathways in sedentary and VWR conditions. These results indicate that hepatic ketogenic deficiency (HMGCS2 KO) diminishes exercise-induced increases in EE and uniquely impacts baseline and exercise-related adaptations in the metabolic and mitochondrial proteome of skeletal muscle.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e0892025"},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13290263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147977529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin receptor signaling in human pathologies: from molecular mechanisms to therapeutic targets.","authors":"Yen-Sung Huang, Sheng-Ding Wu, Hsi-Chih Chen, Kuo-Cheng Lu, Shuk-Man Ka, Chia-Chao Wu","doi":"10.1152/function.011.2026","DOIUrl":"10.1152/function.011.2026","url":null,"abstract":"<p><p>The melatonin receptor 1 A (MTNR1A), a highly conserved G protein-coupled receptor (GPCR), mediates crucial physiological functions. Its structure features an N-terminus responsible for melatonin binding and a C-terminus that initiates downstream signaling pathways to modulate target gene expression. Given MTNR1A's ability to form homodimers or heterodimers with other GPCRs, its expression levels are critical for the precise control of cellular signaling. This review article provides a comprehensive update on MTNR1A, highlighting recent developments concerning its expression distribution, gene regulation, protein motifs, and mediated signaling pathways. We also discuss the clinical relevance of single-nucleotide polymorphisms (SNPs) associated with the MTNR1A receptor and the range of diseases linked to its dysfunction. Current understanding and future perspectives regarding gene regulation and the stimulation of MTNR1A expression are critically addressed. Furthermore, we investigate the role of MTNR1A genetic variants in idiopathic osteoporosis and the association between decreased MTNR1A expression and membranous nephropathy. The systemic involvement of MTNR1A downregulation in cancer, fetal growth restriction, type 2 diabetes, and Parkinson's and Alzheimer's diseases is further underlined by its established biological functions. In conclusion, targeting MTNR1A-related downregulation and developing specific agonists or modulators offer a promising avenue for advancement in therapeutic medicine.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e0112026"},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13245880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147950422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The systems that transport ions and their impact on sperm function and male fertility.","authors":"Mumtarin Jannat Oishee, Beth Baum, Gustavo Blanco","doi":"10.1152/function.083.2025","DOIUrl":"10.1152/function.083.2025","url":null,"abstract":"<p><p>Sperm are highly specialized cells, whose primary function is to transport and deliver the paternal genetic information to the oocyte. Although morphologically complete after being produced in the testis, sperm acquire fertilizing competence through a series of posttesticular maturation steps. During this journey, cues from the surrounding luminal fluids play a crucial role in sperm functional maturation. Among these signals, changes in the ion composition of the extracellular medium are particularly important. Sperm detect these ion fluctuations and regulate their intracellular ion concentrations through membrane ion transport systems. Although some of these transporters are shared with somatic cells, others have evolved as specialized molecular variants uniquely adapted to meet the specific physiological demands of sperm. Genetic mutations and dysfunction of certain ion transporters have been associated with male infertility. Consequently, ion transporters represent promising diagnostic markers for the detection of male infertility and are attractive pharmacological targets for the development of therapies to enhance or inhibit male fertility. This review provides a comprehensive analysis of the ion transport systems that operate in sperm membranes and discusses their function, regulation, and contribution to the overall physiology of sperm.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e0832025"},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13218627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147438209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophages as tissue scavengers, builders, and sensors.","authors":"Luisa Martinez-Pomares","doi":"10.1152/function.108.2025","DOIUrl":"10.1152/function.108.2025","url":null,"abstract":"<p><p>The cellular biology of macrophages underpins the multitude of roles that these cells undertake under homeostatic and inflammatory conditions. Macrophages populate all tissues where they contribute to organ physiology while acting as sensors of health and triggering inflammation in response to organ dysfunction, trauma, and infection. Sharing key characteristics such as a highly developed endocytic compartment, secretion of growth factors and cytokines, motility and antigen presentation, macrophages undergo specific adaptations in each niche guided by environmental clues that result in diverse phenotypes that support tissue-specific roles such as iron recycling, synaptic pruning, bone reabsorption, and processing of lung surfactant. This review will provide an overview of macrophage biology and heterogeneity that underpin their contribution to homeostasis and inflammation to illustrate their importance as therapeutic targets in a wide range of inflammatory diseases.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":"e1082025"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}