Reparative Response Research Articles

I just don’t want to lose face: A self-image reparative response framework of how and when abused subordinates improve their performance

I just don’t want to lose face: A self-image reparative response framework of how and when abused subordinates improve their performance

Pannexin 1 drives efficient epithelial repair after tissue injury.

Epithelial tissues such as lung and skin are exposed to the environment and therefore particularly vulnerable to damage during injury or infection. Rapid repair is therefore essential to restore function and organ homeostasis. Dysregulated epithelial tissue repair occurs in several human disease states, yet how individual cell types communicate and interact to coordinate tissue regeneration is incompletely understood. Here, we show that pannexin 1 (Panx1), a cell membrane channel activated by caspases in dying cells, drives efficient epithelial regeneration after tissue injury by regulating injury-induced epithelial proliferation. Lung airway epithelial injury promotes the Panx1-dependent release of factors including ATP, from dying epithelial cells which regulates macrophage phenotype post-injury. This process, in turn, induces a reparative response in tissue macrophages that includes the induction of the soluble mitogen amphiregulin, which promotes injury-induced epithelial proliferation. Analysis of regenerating lung epithelium identified Panx1-dependent induction of Nras and Bcas2, both of which positively promoted epithelial proliferation and tissue regeneration in vivo. We also established that this role of Panx1 in boosting epithelial repair after injury is conserved between mouse lung and zebrafish tailfin. These data identify a Panx1-mediated communication circuit between epithelial cells and macrophages as a key step in promoting epithelial regeneration post-injury.

Immune and Inflammatory Networks in Myocardial Infarction: Current Research and Its Potential Implications for the Clinic.

Despite recent scientific and technological advances, myocardial infarction (MI) still represents a major global health problem, leading to high morbidity and mortality worldwide. During the post-MI wound healing process, dysregulated immune inflammatory pathways and failure to resolve inflammation are associated with maladaptive left ventricular remodeling, progressive heart failure, and eventually poor outcomes. Given the roles of immune cells in the host response against tissue injury, understanding the involved cellular subsets, sources, and functions is essential for discovering novel therapeutic strategies that preserve the protective immune system and promote optimal healing. This review discusses the cellular effectors and molecular signals across multi-organ systems, which regulate the inflammatory and reparative responses after MI. Additionally, we summarize the recent clinical and preclinical data that propel conceptual revolutions in cardiovascular immunotherapy.

Reparative Reading and the Drug Wars’ Queer Children

This article posits that recent reparative responses to the opioid crisis are consistent with a longer history of reparative hermeneutics conditioned by the drug wars in the Americas, ones that attempt to repair but often reinforce the biopolitical logics produced by the artificial divide between licit and illicit drugs, a distinction that facilitates both racial and imperialist policing and racial capitalist profiteering. The humanities’ postcritical reorientation, and particularly the turn toward the reparative, is underwritten by such relations between state, capital, and drug policy. To investigate the reverberations of such contemporary political and academic investments in drug-war-fueled repair, the article focuses on a recent wave of black fiction and film that reenvisions the 1980s War on Drugs in the era of the opioid epidemic, with particular attention to Barry Jenkins’s film Moonlight (2016) and James Hannaham’s novel Delicious Foods (2015).

Endotypes of Prematurity and Phenotypes of Bronchopulmonary Dysplasia: Toward Personalized Neonatology.

Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, is increasingly recognized as the consequence of a pathological reparative response of the developing lung to both antenatal and postnatal injury. According to this view, the pathogenesis of BPD is multifactorial and heterogeneous with different patterns of antenatal stress (endotypes) that combine with varying postnatal insults and might distinctively damage the development of airways, lung parenchyma, interstitium, lymphatic system, and pulmonary vasculature. This results in different clinical phenotypes of BPD. There is no clear consensus on which are the endotypes of prematurity but the combination of clinical information with placental and bacteriological data enables the identification of two main pathways leading to birth before 32 weeks of gestation: (1) infection/inflammation and (2) dysfunctional placentation. Regarding BPD phenotypes, the following have been proposed: parenchymal, peripheral airway, central airway, interstitial, congestive, vascular, and mixed phenotype. In line with the approach of personalized medicine, endotyping prematurity and phenotyping BPD will facilitate the design of more targeted therapeutic and prognostic approaches.

Chronic liver diseases: From development to novel pharmacological therapies: IUPHAR Review 37.

Chronic liver diseases comprise a broad spectrum of burdensome diseases that still lack effective pharmacological therapies. Our research group focuses on fibrosis, which is a major precursor of liver cirrhosis. Fibrosis consists in a progressive disturbance of liver sinusoidal architecture characterised by connective tissue deposition as a reparative response to tissue injury. Multifactorial events and several types of cells participate in fibrosis initiation and progression, and the process still needs to be completely understood. The development of experimental models of liver fibrosis alongside the identification of critical factors progressing fibrosis to cirrhosis will facilitate the development of more effective therapeutic approaches for such condition. This review provides an overlook of the main process leading to hepatic fibrosis and therapeutic approaches that have emerged from a deep knowledge of the molecular regulation of fibrogenesis in the liver. LINKED ARTICLES: This article is part of a themed issue on Translational Advances in Fibrosis as a Therapeutic Target. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.22/issuetoc.

Properties and Functions of Fibroblasts and Myofibroblasts in Myocardial Infarction

The adult mammalian heart contains abundant interstitial and perivascular fibroblasts that expand following injury and play a reparative role but also contribute to maladaptive fibrotic remodeling. Following myocardial infarction, cardiac fibroblasts undergo dynamic phenotypic transitions, contributing to the regulation of inflammatory, reparative, and angiogenic responses. This review manuscript discusses the mechanisms of regulation, roles and fate of fibroblasts in the infarcted heart. During the inflammatory phase of infarct healing, the release of alarmins by necrotic cells promotes a pro-inflammatory and matrix-degrading fibroblast phenotype that may contribute to leukocyte recruitment. The clearance of dead cells and matrix debris from the infarct stimulates anti-inflammatory pathways and activates transforming growth factor (TGF)-β cascades, resulting in the conversion of fibroblasts to α-smooth muscle actin (α-SMA)-expressing myofibroblasts. Activated myofibroblasts secrete large amounts of matrix proteins and form a collagen-based scar that protects the infarcted ventricle from catastrophic complications, such as cardiac rupture. Moreover, infarct fibroblasts may also contribute to cardiac repair by stimulating angiogenesis. During scar maturation, fibroblasts disassemble α-SMA+ stress fibers and convert to specialized cells that may serve in scar maintenance. The prolonged activation of fibroblasts and myofibroblasts in the infarct border zone and in the remote remodeling myocardium may contribute to adverse remodeling and to the pathogenesis of heart failure. In addition to their phenotypic plasticity, fibroblasts exhibit remarkable heterogeneity. Subsets with distinct phenotypic profiles may be responsible for the wide range of functions of fibroblast populations in infarcted and remodeling hearts.

Early Protective Role of Inflammation in Cardiac Remodeling and Heart Failure: Focus on TNFα and Resident Macrophages.

Cardiac hypertrophy, initiated by a variety of physiological or pathological stimuli (hemodynamic or hormonal stimulation or infarction), is a critical early adaptive compensatory response of the heart. The structural basis of the progression from compensated hypertrophy to pathological hypertrophy and heart failure is still largely unknown. In most cases, early activation of an inflammatory program reflects a reparative or protective response to other primary injurious processes. Later on, regardless of the underlying etiology, heart failure is always associated with both local and systemic activation of inflammatory signaling cascades. Cardiac macrophages are nodal regulators of inflammation. Resident macrophages mostly attenuate cardiac injury by secreting cytoprotective factors (cytokines, chemokines, and growth factors), scavenging damaged cells or mitochondrial debris, and regulating cardiac conduction, angiogenesis, lymphangiogenesis, and fibrosis. In contrast, excessive recruitment of monocyte-derived inflammatory macrophages largely contributes to the transition to heart failure. The current review examines the ambivalent role of inflammation (mainly TNFα-related) and cardiac macrophages (Mφ) in pathophysiologies from non-infarction origin, focusing on the protective signaling processes. Our objective is to illustrate how harnessing this knowledge could pave the way for innovative therapeutics in patients with heart failure.

Plasma Lipid Profiles Change with Increasing Numbers of Mild Traumatic Brain Injuries in Rats.

Mild traumatic brain injury (mTBI) causes structural, cellular and biochemical alterations which are difficult to detect in the brain and may persist chronically following single or repeated injury. Lipids are abundant in the brain and readily cross the blood-brain barrier, suggesting that lipidomic analysis of blood samples may provide valuable insight into the neuropathological state. This study used liquid chromatography-mass spectrometry (LC-MS) to examine plasma lipid concentrations at 11 days following sham (no injury), one (1×) or two (2×) mTBI in rats. Eighteen lipid species were identified that distinguished between sham, 1× and 2× mTBI. Three distinct patterns were found: (1) lipids that were altered significantly in concentration after either 1× or 2× F mTBI: cholesterol ester CE (14:0) (increased), phosphoserine PS (14:0/18:2) and hexosylceramide HCER (d18:0/26:0) (decreased), phosphoinositol PI(16:0/18:2) (increased with 1×, decreased with 2× mTBI); (2) lipids that were altered in response to 1× mTBI only: free fatty acid FFA (18:3 and 20:3) (increased); (3) lipids that were altered in response to 2× mTBI only: HCER (22:0), phosphoethanolamine PE (P-18:1/20:4 and P-18:0/20:1) (increased), lysophosphatidylethanolamine LPE (20:1), phosphocholine PC (20:0/22:4), PI (18:1/18:2 and 20:0/18:2) (decreased). These findings suggest that increasing numbers of mTBI induce a range of changes dependent upon the lipid species, which likely reflect a balance of damage and reparative responses.

Identification of macrophages in normal and injured mouse tissues using reporter lines and antibodies

Reliable tools for macrophage identification in mouse tissues are critical for studies investigating inflammatory and reparative responses. Transgenic reporter mice and anti-macrophage antibodies have been used as “specific pan-macrophage” markers in many studies; however, organ-specific patterns of expression and non-specific labeling of other cell types, such as fibroblasts, may limit their usefulness. Our study provides a systematic comparison of macrophage labeling patterns in normal and injured mouse tissues, using the CX3CR1 and CSF1R macrophage reporter lines and anti-macrophage antibodies. Moreover, we tested the specificity of macrophage antibodies using the fibroblast-specific PDGFRmathrm{alpha } reporter line. Mouse macrophages exhibit organ-specific differences in expression of macrophage markers. Hepatic macrophages are labeled for CSF1R, Mac2 and F4/80, but lack CX3CR1 expression, whereas in the lung, the CSF1R+/Mac2+/Mac3+ macrophage population is not labeled with F4/80. In the splenic red pulp, subpopulations of CSF1R+/F4/80+/Mac3+cells were labeled with Mac2, CX3CR1 and lysozyme M. In the kidney, Mac2, Mac3 and lysozyme M labeled a fraction of the CSF1R+ and CX3CR1+ macrophages, but also stained tubular epithelial cells. In normal hearts, the majority of CSF1R+ and CX3CR1+ cells were not detected with anti-macrophage antibodies. Myocardial infarction was associated with marked expansion of the CSF1R+ and CX3CR1+ populations that peaked during the proliferative phase of cardiac repair, and also expressed Mac2, Mac3 and lysozyme M. In normal mouse tissues, a small fraction of cells labeled with anti-macrophage antibodies were identified as PDGFRmathrm{alpha }+ fibroblasts, using a reporter system. The population of PDGFRmathrm{alpha }+ cells expressing macrophage markers expanded following injury, likely reflecting emergence of cellular phenotypes with both fibroblast and macrophage characteristics. In conclusion, mouse macrophages exhibit remarkable heterogeneity. Selection of the most appropriate markers for identification of macrophages in mouse tissues is dependent on the organ and the pathologic condition studied.

Non-Coding RNAs: Prevention, Diagnosis, and Treatment in Myocardial Ischemia-Reperfusion Injury.

Recent knowledge concerning the role of non-coding RNAs (ncRNAs) in myocardial ischemia/reperfusion (I/R) injury provides new insight into their possible roles as specific biomarkers for early diagnosis, prognosis, and treatment. MicroRNAs (miRNAs) have fewer than 200 nucleotides, while long ncRNAs (lncRNAs) have more than 200 nucleotides. The three types of ncRNAs (miRNAs, lncRNAs, and circRNAs) act as signaling molecules strongly involved in cardiovascular disorders (CVD). I/R injury of the heart is the main CVD correlated with acute myocardial infarction (AMI), cardiac surgery, and transplantation. The expression levels of many ncRNAs and miRNAs are highly modified in the plasma of MI patients, and thus they have the potential to diagnose and treat MI. Cardiomyocyte and endothelial cell death is the major trigger for myocardial ischemia–reperfusion syndrome (MIRS). The cardioprotective effect of inflammasome activation in MIRS and the therapeutics targeting the reparative response could prevent progressive post-infarction heart failure. Moreover, the pharmacological and genetic modulation of these ncRNAs has the therapeutic potential to improve clinical outcomes in AMI patients.

Leptin in Dental Pulp and Periapical Tissues: A Narrative Review.

Leptin is a non-glycosylated 16 kDa protein synthesized mainly in adipose cells. The main function of leptin is to regulate energy homeostasis and weight control in a central manner. There is increasing evidence that leptin also has systemic effects, acting as a link between innate and acquired immune responses. The expression of leptin and its receptor in human dental pulp and periradicular tissues have already been described, as well as several stimulatory effects of leptin protein expression in dental and periodontal tissues. The aim of this paper was to review and to compile the reported scientific literature on the role and effects of leptin in the dental pulp and periapical tissues. Twelve articles accomplished the inclusion criteria, and a comprehensive narrative review was carried out. Review of the available scientific literature concluded that leptin has the following effects on pulpal and periapical physiology: 1) Stimulates odontogenic differentiation of dental pulp stem cells (DPSCs), 2) Increases the expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1), odontoblastic proteins involved in odontoblastic differentiation and dentin mineralization, 3) Stimulates vascular endothelial growth factor (VEGF) expression in human dental pulp tissue and primary cultured cells of human dental pulp (hDPCs), 4) Stimulates angiogenesis in rat dental pulp cells, and 5) Induces the expression of interleucinas 6 and 8 in human periodontal ligament cells (hPDLCs). There is evidence which suggests that leptin is implicated in the dentin mineralization process and in pulpal and periapical inflammatory and reparative responses.

HMGB1-Mediated Activation of the Inflammatory-Reparative Response Following Myocardial Infarction.

Different cell types belonging to the innate and adaptive immune system play mutually non-exclusive roles during the different phases of the inflammatory-reparative response that occurs following myocardial infarction. A timely and finely regulation of their action is fundamental for the process to properly proceed. The high-mobility group box 1 (HMGB1), a highly conserved nuclear protein that in the extracellular space can act as a damage-associated molecular pattern (DAMP) involved in a large variety of different processes, such as inflammation, migration, invasion, proliferation, differentiation, and tissue regeneration, has recently emerged as a possible regulator of the activity of different immune cell types in the distinct phases of the inflammatory reparative process. Moreover, by activating endogenous stem cells, inducing endothelial cells, and by modulating cardiac fibroblast activity, HMGB1 could represent a master regulator of the inflammatory and reparative responses following MI. In this review, we will provide an overview of cellular effectors involved in these processes and how HMGB1 intervenes in regulating each of them. Moreover, we will summarize HMGB1 roles in regulating other cell types that are involved in the different phases of the inflammatory-reparative response, discussing how its redox status could affect its activity.

Features of repair processes and immune response of laboratory animals body to fluoroplast-4 implantation in experiment

The paper analyzes the features of the reparative and immune response of the body during the replacement of subcutaneous soft tissue defects in the early postoperative period. The restoration of a muscle defect and links of the immune system was established.

The Effect of Fluence on Neutrophil Kinetics in Zebrafish Wounds Using Real-time In Vivo Imaging

Background: Neutrophils participate in a cooperative defense strategy with macrophages following tissue injury. Application of low dose electromagnetic radiation via 635 nm wavelength can enhance macrophage recruitment to the wound, decrease tissue levels of ROS and speed healing. The impact of this wavelength on neutrophil activity in vivo is not well-described. Given that wound healing can be enhanced if collateral damage by neutrophils within the wound is decreased, we investigated how neutrophil kinetics changed during these accelerated reparative responses. Methods: Zebrafish, transgenic for the fluorescent neutrophil marker, mpx-dendra2, underwent defined fin tissue injury, and were randomized to one of two laser treatment groups, 3 J/cm2 (n=57), or 18 J/cm2 (n=69) or to the control group, 0 J/cm2 (n=164). Electromagnetic wave exposures were administered by a 635-nm continuous 5mW He:Ne laser with recipients randomized by dose delivered. Fish were three-dimensionally time-lapse imaged 30-120 minutes post injury (mpi) and wound healing documented at 24 hours post-injury. Individual neutrophil movement was tracked according to distance from wound center. Results: The lower treatment fluence, 3 J/cm2, significantly decreased neutrophil migration speed into the wound, increased reverse migration, and promoted stasis outside the adjacent wound area when compared to control and higher energy doses. The 3 J/cm2 treatment groups also exhibited more rapid wound closure when compared to control or higher fluence. Conclusions: Unlike our previous work in macrophages in which low fluence treatment enhanced the speed of forward directed migration into the wound, the response of neutrophils was decreased speed into the wound, increased reverse migration, and stasis outside the areas of the wound edges. These findings advance the notion that low fluence treatments reduce neutrophil inflammatory responses within the wound by their reduced presence within the wound. Reduced neutrophil-mediated collateral damage may work in concert with enhanced macrophage wound activity to promote faster wound healing.

Mechanobiological Strategies to Enhance Stem Cell Functionality for Regenerative Medicine and Tissue Engineering.

Stem cells have been extensively used in regenerative medicine and tissue engineering; however, they often lose their functionality because of the inflammatory microenvironment. This leads to their poor survival, retention, and engraftment at transplantation sites. Considering the rapid loss of transplanted cells due to poor cell-cell and cell-extracellular matrix (ECM) interactions during transplantation, it has been reasoned that stem cells mainly mediate reparative responses via paracrine mechanisms, including the secretion of extracellular vesicles (EVs). Ameliorating poor cell-cell and cell-ECM interactions may obviate the limitations associated with the poor retention and engraftment of transplanted cells and enable them to mediate tissue repair through the sustained and localized presentation of secreted bioactive cues. Biomaterial-mediated strategies may be leveraged to confer stem cells enhanced immunomodulatory properties, as well as better engraftment and retention at the target site. In these approaches, biomaterials have been exploited to spatiotemporally present bioactive cues to stem cell-laden platforms (e.g., aggregates, microtissues, and tissue-engineered constructs). An array of biomaterials, such as nanoparticles, hydrogels, and scaffolds, has been exploited to facilitate stem cells function at the target site. Additionally, biomaterials can be harnessed to suppress the inflammatory microenvironment to induce enhanced tissue repair. In this review, we summarize biomaterial-based platforms that impact stem cell function for better tissue repair that may have broader implications for the treatment of various diseases as well as tissue regeneration.

Nanofat: A therapeutic paradigm in regenerative medicine.

Adipose tissue is a compact and well-organized tissue containing a heterogeneous cellular population of progenitor cells, including mesenchymal stromal cells. Due to its availability and accessibility, adipose tissue is considered a “stem cell depot.” Adipose tissue products possess anti-inflammatory, anti-fibrotic, anti-apoptotic, and immunomodulatory effects. Nanofat, being a compact bundle of stem cells with regenerative and tissue remodeling potential, has potential in translational and regenerative medicine. Considering the wide range of applicability of its reconstructive and regenerative potential, the applications of nanofat can be used in various disciplines. Nanofat behaves on the line of adipose tissue-derived mesenchymal stromal cells. At the site of injury, these stromal cells initiate a site-specific reparative response comprised of remodeling of the extracellular matrix, enhanced and sustained angiogenesis, and immune system modulation. These properties of stromal cells provide a platform for the usage of regenerative medicine principles in curbing various diseases. Details about nanofat, including various preparation methods, characterization, delivery methods, evidence on practical applications, and ethical concerns are included in this review. However, appropriate guidelines and preparation protocols for its optimal use in a wide range of clinical applications have yet to be standardized.

Segmental Arterial Mediolysis: A Multiguised Vasospastic Arteriopathy with Collateral Mesangial Cell Hyperplasia and Cardiac Toxicity Generated by Norepinephrine and Hyperdense Adrenoceptors Alone or by Crosstalk with Other Pressor Agents.

Segmental arterial mediolysis (SAM), an uncommon vasospastic arteriopathy occurring in the muscular arteries innervated by the peripheral sympathetic nervous system, usually presents with catastrophic abdominal and retroperitoneal hemorrhages in elderly patients. SAM is initiated by the coupling of norepinephrine to plastically derived hyperdense foci of alpha-1 adrenergic receptors on the sarcolemma of arterial muscle. This ligand is created by stimuli signaled by iatrogenic sympathomimetic agonists, some beta-2 agonists, or an excessive release of adrenal catecholamines. Coupling of this ligand with cytoplasmic heterotrimeric Gq protein excessively signals a cascade of biochemical events generating two principal lesions of injurious-phase SAM—the shearing of the outer media from the adventitia and an overload of cytoplasmic calcium ions toxic to mitochondria causing mediolysis and/or apoptosis. The massive hemorrhages are caused by ruptured gap aneurysms created by the transmedial loss of the medial muscle. A norepinephrine-directed reparative response rapidly develops either resolving angiographic injurious lesions or creating a body of vascular disorders, the new guises of SAM with ischemic clinical profiles. These present in the epicardial, vertebral, intestinal, and retroperitoneal arteries, often in younger females as fibromuscular dysplasia, dissecting hematomas, and persistent aneurysms. Norepinephrine can crosstalk with other pressor agents to create SAM lesions—serotonin with idiopathic pulmonary hypertension and persistent pulmonary hypertension in the newborn, histamine in spontaneous coronary artery dissections with eosinophilia, and endothelin-1 in a field effect generated by SAM that creates venous fibromuscular dysplasia. Norepinephrine also participates in the collateral development of mesangial hyperplasia with focal segmental glomerulosclerosis and myocardial mediolysis and apoptosis in subjects with markedly elevated heart rates. Conclusion. Norepinephrine coupling with plastically elevated alpha-1 adrenoceptor or other pressor agents generates SAM, a histologically recognizable vasospastic arteriopathy, that with repair is transformed into several different standardized arterial diseases that alter SAM's clinical profile from a hemorrhagic to an ischemic disorder.

Progression and Resolution of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Golden Syrian Hamsters

To catalyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research, including development of novel interventive and preventive strategies, the progression of disease was characterized in a robust coronavirus disease 2019 (COVID-19) animal model. In this model, male and female golden Syrian hamsters were inoculated intranasally with SARS-CoV-2 USA-WA1/2020. Groups of inoculated and mock-inoculated uninfected control animals were euthanized at 2, 4, 7, 14, and 28 days after inoculation to track multiple clinical, pathology, virology, and immunology outcomes. SARS-CoV-2–inoculated animals consistently lost body weight during the first week of infection, had higher lung weights at terminal time points, and developed lung consolidation per histopathology and quantitative image analysis measurements. High levels of infectious virus and viral RNA were reliably present in the respiratory tract at days 2 and 4 after inoculation, corresponding with widespread necrosis and inflammation. At day 7, when the presence of infectious virus was rare, interstitial and alveolar macrophage infiltrates and marked reparative epithelial responses (type II hyperplasia) dominated in the lung. These lesions resolved over time, with only residual epithelial repair evident by day 28 after inoculation. The use of quantitative approaches to measure cellular and morphologic alterations in the lung provides valuable outcome measures for developing therapeutic and preventive interventions for COVID-19 using the hamster COVID-19 model.

Early-life inflammation primes a T helper 2 cell-fibroblast niche in skin.

Inflammation early in life can prime the local immune milieu of peripheral tissues, which can cause lasting changes in immunological tone that confer disease protection or susceptibility1. The cellular and molecular mechanisms that prompt changes in immune tone in many nonlymphoid tissues remain largely unknown. Here we find that time-limited neonatal inflammation induced by a transient reduction in neonatal regulatory T cells causes a dysregulation of subcutaneous tissue in mouse skin. This is accompanied by the selective accumulation of type 2 helperT (TH2) cells within a distinct microanatomical niche. TH2 cells are maintained into adulthood through interactions with a fibroblast population in skin fascia that we refer to asTH2-interacting fascial fibroblasts (TIFFs), which expand in response to TH2 cytokines to form subcutaneous fibrous bands. Activation of the TH2-TIFF niche due to neonatal inflammation primes the skin for altered reparative responses to wounding. Furthermore, we identify fibroblasts in healthy human skin that express the TIFF transcriptional signature and detect these cells athigh levels in eosinophilic fasciitis, an orphan disease characterized by inflammation and fibrosis of the skin fascia. Taken together, these data define a previously unidentified TH2 cell niche in skin and functionally characterize a disease-associated fibroblast population. The results also suggest a mechanism of immunological priming whereby inflammation early in life creates networks between adaptive immune cells and stromal cells to establish an immunological set-point in tissues that is maintained throughout life.