Recurrence of Glandular Odontogenic Cysts: A Systematic Review.

BACKGROUND: The glandular odontogenic cyst (GOC) is a benign developmental cyst of the jaws that is characterized by a high recurrence rate. METHODS: A systematic review is presented of reported cases, case series, and retrospective studies of recurrent cases of glandular odontogenic cysts, to determine the overall and detailed demographic features with documentation of the specific histologic features of the initial presentation of each cyst. Searches of detailed databases were carried out to identify articles published in the English language from 1988 to 2023. The variables were demographics, patient symptoms, cyst location, radiographic features, histopathological findings, type of treatment, and minimum eight months of follow-up. RESULTS: Eighteen cases were identified: with an equal gender presentation of 50% females and 50% males. The average age was 44.7. The mean size was 3.5 cm. The most common location was in the anterior mandible in 50% (n = 9) of cases, followed by the posterior mandible 27.8% (n = 5). Most patients were asymptomatic 55.6% (n = 10). The most common histologic features at first diagnosis were mucous cells in 88.9% (n = 16), variable thickness with 83.3% (n = 15), eosinophilic cuboidal cells 88.9% (n = 16), microcysts 83.3% (n = 15), and clear cells 77.8% (n = 14) cases. CONCLUSION: GOC has an aggressive behavior. Evidence was not conclusive to link any single or combination of histologic features to recurrence, and the strongest correlation for recurrence was the type of treatment. Since this is an uncommon cyst, more cases are needed. Follow-up should continue for at least five years, because recurrences were higher between years 3 and 5.

A single-cell atlas of IL-23 inhibition in cutaneous psoriasis distinguishes clinical response.

Psoriasis vulgaris and other chronic inflammatory diseases improve markedly with therapeutic blockade of interleukin-23 (IL-23) signaling, but the genetic mechanisms underlying clinical responses remain poorly understood. Using single-cell transcriptomics, we profiled immune cells isolated from lesional psoriatic skin before and during IL-23 blockade. In clinically responsive patients, a psoriatic transcriptional signature in skin-resident memory T cells was strongly attenuated. In contrast, poorly responsive patients were distinguished by persistent activation of IL-17-producing T (T17) cells, a mechanism distinct from alternative cytokine signaling or resistance isolated to epidermal keratinocytes. Even in IL-23 blockade-responsive patients, we detected a recurring set of recalcitrant, disease-specific transcriptional abnormalities. This irreversible immunological state may necessitate ongoing IL-23 inhibition. Spatial transcriptomic analyses also suggested that successful IL-23 blockade requires dampening of >90% of IL-17-induced response in lymphocyte-adjacent keratinocytes, an unexpectedly high threshold. Collectively, our data establish a patient-level paradigm for dissecting responses to immunomodulatory treatments.

Regulatory T cells in skin mediate immune privilege of the hair follicle stem cell niche.

Immune tolerance is maintained in lymphoid organs (LOs). Despite the presence of complex immune cell networks in non-LOs, it is unknown whether self-tolerance is maintained in these tissues. We developed a technique to restrict genetic recombination to regulatory T cells (Tregs) only in skin. Selective depletion of skin Tregs resulted in T cell-mediated inflammation of hair follicles (HFs). Suppression did not rely on CTLA-4, but instead on high-affinity interleukin-2 (IL-2) receptor expression by skin Tregs, functioning exclusively in a cell-extrinsic manner. In a novel model of HF stem cell (HFSC)-driven autoimmunity, we reveal that skin Tregs immunologically protect the HFSC niche. Finally, we used spatial transcriptomics to identify aberrant IL-2 signaling at stromal-HF interfaces in a rare form of human alopecia characterized by HFSC destruction and alopecia areata. Collectively, these results reveal the fundamental biology of Tregs in skin uncoupled from the systemic pool and elucidate a mechanism of self-tolerance.

Gnathic Schwannomas: A Report of Two Cases and Systematic Review of the Literature.

BACKGROUND: The intraosseous schwannoma (IS) is a benign peripheral nerve sheath tumor postulated to arise de novo or from nerve fibers in preexisting nutrient canals. ISs are uncommon and comprise less than 1% of neoplasms originating in bone. We herein present two cases of mandibular schwannomas-the first case was a 66-year-old female with a four-month history of pain and pressure associated with an anterior mandibular radiolucency, and the second case was an asymptomatic 12-year-old female with separate radiolucencies of her mandibular symphysis and right posterior mandible. Incisional biopsies of all three lesions showed a benign spindle cell neoplasm with histologic features of a schwannoma; the tumor cells were strongly reactive for S-100. The patients underwent complete enucleation of their lesions and are without evidence of disease at ten months and five years, respectively. METHODS: A systematic review was undertaken to evaluate the diagnostic features, treatment, and patient outcomes of gnathic schwannomas. RESULTS: A total of 93 cases were identified with the following demographic findings: predominance in females (57%); average age of occurrence of 37.3 years (8 to 77 years); mean size of 3.6 cm; and involvement of the mandibular body (37.6%), mandibular body and ramus (18.3%), and anterior mandible (18.3%). The predominant clinical sign was swelling (69.9%), and the most common radiographic presentation was a radiolucency (94.6%) with well-defined borders (72%). CONCLUSION: All cases were treated surgically, with an average follow-up interval of 22.9 months and a recurrence rate of 5.4.

Hereditary hemochromatosis: An update vision of the laboratory diagnosis.

Haemochromatosis (HC) is an inherited disorder of iron metabolism. The 85-90% of Hereditary hemochromatosis cases are caused by mutations in HFE gene (HC type 1). The remaining 10-15% of HC cases are caused by mutations in other non-HFE genes (HJV, HAMP, TRF2, SLC40A1, BMP6). The study of patients for the diagnosis of HC has an important laboratory approached: analysis of biochemical parameters and genetic studies. To confirm a case, it is necessary to carry out a genetic study of the C282Y and H63D mutations. The presence of C282Y mutation in homozygosis is compatible with the diagnosis of HC type 1. Due to the incomplete penetrance of this mutation and the variable phenotypic expression, the severe forms of the disease are relatively rare. The study of variants in non-HFE genes allows more detailed study of both non-classic HC cases and those with more severe clinical expression. The genotype characterization of a patient not always justified the phenotype expression of the symptoms in this disease. All laboratory clinicians must consider recommendation provide by the experts in the Materia.

Reassessment of the extinction risk status of the ponytail palm Beaucarnea inermis / Reevaluación del riesgo de extinción de la pata de elefante Beaucarnea inermis

Abstract Beaucarnea inermis is an endemic species from Northeast Mexico, in the states of San Luis Potosí and Tamaulipas. It is appreciated as an ornamental plant, so its populations are subject to the poaching of individuals for illegal trade. Previous studies determined that their populations have been affected due to the disturbance since the incidence of anthropogenic activities affects the viability of the species. Here we determine the current conservation status of B. inermis and identify their main risk factor by performing an extinction risk assessment based on the Annex II "Method for Evaluation of Risk of Extinction of Plants in Mexico". We studied 10 populations of B. inermis from protected and non-protected areas in San Luis Potosí and Tamaulipas. We considered the MER criteria: A) geographical distribution characteristics, B) habitat characteristics, C) intrinsic biological vulnerability, and D) impact of human activity. Using field and analyzed data, the MER assessment gives 1.91 points that confirm B. inermis is correctly classified as an Endangered species. The natural protected areas where the species occurs represent cores for its protection; however, the surface of these areas may not be sufficient without biological corridors that connect them.

Resumen Beaucarnea inermis es una especie endémica del Noroeste de México distribuida en los estados de San Luis Potosí y Tamaulipas. Es apreciada como planta ornamental, por lo que sus poblaciones están sujetas al saqueo de individuos para su comercialización ilegal. En trabajos anteriores se determinó que sus poblaciones han sido afectadas debido al disturbio por la incidencia de actividades antrópicas que afectan su viabilidad. En la presente contribución se determina el nivel de riesgo de B. inermis con base en el Anexo Normativo II "Método de Evaluación de Riesgo de Extinción de Plantas en México". Se estudiaron 10 poblaciones de B. inermis en San Luis Potosí y Tamaulipas, tanto en áreas naturales protegidas como en sitios no protegidos. Los criterios MER considerados fueron: A) características de la distribución geográfica, B) características del hábitat, C) vulnerabilidad biológica intrínseca y D) impacto de la actividad humana. El análisis MER arroja un valor de 1.91 que, confirma a B. inermis dentro de la categoría de Amenazada. Las áreas naturales protegidas donde se distribuye la especie funcionan como núcleos de protección, sin embargo, su superficie puede no ser suficiente sin la presencia de corredores biológicos que las conecten.

In vitro antimicrobial effect of essential tea tree oil(Melaleuca alternifolia), thymol, and carvacrol on microorganisms isolated from cases of bovine clinical mastitis.

Both Gram-negative and Gram-positive bacteria have recently developed antibiotic resistance to treatments for bovine mastitis, creating a serious concern for public and animal health. The objective of this study was to analyse in vitro microbicidal activity of tea tree oil, thymol and carvacrol (composed of oregano and thyme essential oils) on bacteria isolated from clinical mastitis. Field isolates and ATCC strains of the Staphylococcus spp, Streptococcus spp, Escherichia coli, Klebsiella pneumoniae, and Candida albicans genera were analysed. The agar diffusion technique was used to test bactericidal susceptibility and plate microdilution was utilized to determine the minimum inhibitory, bactericidal, and fractional inhibitory concentrations. Thymol alone and the combinations of thymol-carvacrol and thymol-TTO obtained the highest inhibition diameters for Gram-negative bacteria, while for Gram-positive bacteria and C. albicans, thymol and the combination thymol-carvacrol obtained the highest indices. TTO, thymol, and carvacrol had MIC values of 1.56-25 mg/ml, 0.05-0.4 mg/ml, and 0.02-0.2 mg/ml, respectively. CMB results for the Gram-negative and gram-positive groups were 0.39-0.78 mg/ml, and for C. albicans, 0.78-1.56 mg/ml. Results for the fractional inhibitory concentrations show that the TTO+thymol and thymol+carvacrol combinations had additive activity against groups of Gram-negative bacteria and C. albicans. These natural components, evaluated individually and in combinations, have an effectiveness above 70%.

Innate type 2 immunity controls hair follicle commensalism by Demodex mites.

Demodex mites are commensal parasites of hair follicles (HFs). Normally asymptomatic, inflammatory outgrowth of mites can accompany malnutrition, immune dysfunction, and aging, but mechanisms restricting Demodex outgrowth are not defined. Here, we show that control of mite HF colonization in mice required group 2 innate lymphoid cells (ILC2s), interleukin-13 (IL-13), and its receptor, IL-4Ra-IL-13Ra1. HF-associated ILC2s elaborated IL-13 that attenuated HFs and epithelial proliferation at anagen onset; in their absence, Demodex colonization led to increased epithelial proliferation and replacement of gene programs for repair by aberrant inflammation, leading to the loss of barrier function and HF exhaustion. Humans with rhinophymatous acne rosacea, an inflammatory condition associated with Demodex, had increased HF inflammation with decreased type 2 cytokines, consistent with the inverse relationship seen in mice. Our studies uncover a key role for skin ILC2s and IL-13, which comprise an immune checkpoint that sustains cutaneous integrity and restricts pathologic infestation by colonizing HF mites.

Classification of human chronic inflammatory skin disease based on single-cell immune profiling.

Inflammatory conditions represent the largest class of chronic skin disease, but the molecular dysregulation underlying many individual cases remains unclear. Single-cell RNA sequencing (scRNA-seq) has increased precision in dissecting the complex mixture of immune and stromal cell perturbations in inflammatory skin disease states. We single-cell-profiled CD45+ immune cell transcriptomes from skin samples of 31 patients (7 atopic dermatitis, 8 psoriasis vulgaris, 2 lichen planus (LP), 1 bullous pemphigoid (BP), 6 clinical/histopathologically indeterminate rashes, and 7 healthy controls). Our data revealed active proliferative expansion of the Treg and Trm components and universal T cell exhaustion in human rashes, with a relative attenuation of antigen-presenting cells. Skin-resident memory T cells showed the greatest transcriptional dysregulation in both atopic dermatitis and psoriasis, whereas atopic dermatitis also demonstrated recurrent abnormalities in ILC and CD8+ cytotoxic lymphocytes. Transcript signatures differentiating these rash types included genes previously implicated in T helper cell (TH2)/TH17 diatheses, segregated in unbiased functional networks, and accurately identified disease class in untrained validation data sets. These gene signatures were able to classify clinicopathologically ambiguous rashes with diagnoses consistent with therapeutic response. Thus, we have defined major classes of human inflammatory skin disease at the molecular level and described a quantitative method to classify indeterminate instances of pathologic inflammation. To make this approach accessible to the scientific community, we created a proof-of-principle web interface (RashX), where scientists and clinicians can visualize their patient-level rash scRNA-seq-derived data in the context of our TH2/TH17 transcriptional framework.

Bile acid-sensitive tuft cells regulate biliary neutrophil influx.

Inflammation and dysfunction of the extrahepatic biliary tree are common causes of human pathology, including gallstones and cholangiocarcinoma. Despite this, we know little about the local regulation of biliary inflammation. Tuft cells, rare sensory epithelial cells, are particularly prevalent in the mucosa of the gallbladder and extrahepatic bile ducts. Here, we show that biliary tuft cells express a core genetic tuft cell program in addition to a tissue-specific gene signature and, in contrast to small intestinal tuft cells, decreased postnatally, coincident with maturation of bile acid production. Manipulation of enterohepatic bile acid recirculation revealed that tuft cell abundance is negatively regulated by bile acids, including in a model of obstructive cholestasis in which inflammatory infiltration of the biliary tree correlated with loss of tuft cells. Unexpectedly, tuft cell-deficient mice spontaneously displayed an increased gallbladder epithelial inflammatory gene signature accompanied by neutrophil infiltration that was modulated by the microbiome. We propose that biliary tuft cells function as bile acid-sensitive negative regulators of inflammation in biliary tissues and serve to limit inflammation under homeostatic conditions.

Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19

Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease including MIS-C and chilblain-like lesions (CLL), otherwise known as "COVID toes", remains unclear. Studying multinational cohorts, we found that, in CLL, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs post-disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19-affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased levels of NETs when compared to other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients. SummaryNET formation and degradation are dysregulated in pediatric and symptomatic adult patients with various complications of COVID-19, in association with disease severity. NET degradation impairments are multifactorial and associated with natural inhibitors of DNase 1, G-actin and anti-DNase1L3 and anti-NET antibodies. Infection with the Omicron variant is associated with decreased levels of NETs when compared to other SARS-CoV-2 strains.

ILC2s - development, divergence, dispersal.

Over the last decade, we have come to appreciate group 2 innate lymphoid cells (ILC2s) as important players in host and tissue immunity. New studies of ILC2s and their precursors using novel reporter mice, advanced microscopy, and multi-omics approaches have expanded our knowledge on how these cells contribute to tissue physiology and function. This review highlights recent literature on this enigmatic cell, and we organize our discussion across three important paradigms in ILC2 biology: development, divergence, and dispersal. In addition, we frame our discussion in the context of other innate and adaptive immune cells to emphasize the relevance of expanding knowledge of ILC2s and tissue immunity.

Clear Cell Odontogenic Carcinoma a Systematic Review.

Clear cell Odontogenic Carcinoma (CCOC) is an uncommon malignant odontogenic tumor (MOT). It is the fifth most common MOT. A systematic review is presented of reported cases, case series and retrospective studies of CCOC, to determine trends in presentation, diagnostic features, treatment, and patient outcome. Searches of detailed databases were carried out to identify papers reporting CCOC. The variables were demographics, patient symptoms, tumor location, histopathological findings, immunohistochemical studies, treatment, follow-up, and recurrence. 117 cases were identified; CCOC was most frequently seen in mature females 65% (n = 76). The total average age was 55.4 with a range from 17 to 89 years, for females 56.4 and males 53.6 years. The mean size was 3.41 cm. The most common location was in the mandibular body 36.2% (n = 42), followed by the anterior mandible 23.3% (n = 27). The most common clinical presentation was a swelling 80.4% (n = 74), and the main symptom was pain 41.3% (n = 31), followed by painless lesion 24% (n = 18). The most common Immunohistochemistry positive expression was CK19, EMA, and CEA, and for special staining periodic acid Shiff (PAS); 97% of cases were treated surgically. The average follow-up was 30.3 months, and recurrence was reported in 52.4% of the cases. Conclusion: CCOC shows a strong predilection for the body and anterior mandible, and females are more frequently affected. CCOCs can be painful and the principle clinical sign is swelling, CCOCs can metastasize, and the prognosis is fair.

Metastasis to the oral and maxillofacial region. A systematic review.

OBJECTIVE: Metastasis to oral and maxillofacial region (MOMFR) is an unusual finding; representing between 1 and 1.5% of all malignancies in the maxillofacial region. A systematic review is presented to determine trends in presentation, diagnostic features, and patient outcome. METHODS: Searches of databases were carried out for papers reporting MOMFR. The variables were demographics, patient symptoms, tumor location, tumor size, histopathology, origin of the tumor, immunohistochemical studies, follow-up and survival. RESULTS: 696 cases were identified; 391 males, and 305 females. The most common race was white. The most common primary tumor for females was from breast 31.1% (n = 95), for males from lung 20.5% (n = 143). The most common location was the mandible 44.9% (n = 313), followed by gingival soft tissue 16.8% (n = 117). A frequent clinical symptom was pain with 17.5% (n = 122). The most common clinical presentation was a mass or tumor 37.4% (n = 260). The mean age was 58.8 years. The average time before diagnosis was 10.3 months, the mean follow-up after diagnosis was 13.1 months, and the average survival was 9.8 months. CONCLUSION: MOMFR shows a strong predilection for the posterior mandible, with a mass or tumor being the most common clinical presentation. They are frequently painful, and demonstrate a poor prognosis.

A novel dual nerve transfer for restoration of shoulder function and sensory recovery of the hand, in patients with C567 traumatic root avulsion of the brachial plexus.

OBJECTIVE: The objective of our study is to determine the anatomical viability in cadavers of a novel doble nerve transfer technique for simultaneous reanimation of shoulder abduction and sensory recovery of the hand, in patients with brachial plexus injuries sustaining a C5-C6-C7 roots avulsion. These new transfers should be complemented in the clinical setting with other classic nerve transfers, i.e.: (1) a spinal accessory to suprascapular for shoulder abduction and stability, (2) ulnar nerve fascicles to the biceps branches of the musculocutaneous for elbow flexion, and (3) intercostal to triceps branches for elbow extension. METHODS: The proposed surgical technique includes (1) transferring motor fascicles of the median nerve (MNF), as donors to the axillary nerve (AN), and (2) the whole medial antebrachial cutaneous nerve (MACN) to the lateral contribution (sensory) of the median nerve (LCMN), both without the use of interposed nerve grafts. These techniques were performed in eight cadaveric upper extremities. Analyzed variables were: donor and receptor nerves diameter, length and distance of donor and receptors nerves, and axonal count. RESULTS: The mean distance between the MNF and its point of coaptation to the AN was 19 mm. The average length of each one of the MNF, after distal dissection, was 46.5 mm. The average diameter of each fascicle of the median nerve at its coaptation point with the axillary nerve was 0.8 mm, while the average diameter of the latter was 3.9 mm. The average distance between the MACN and its point of coaptation to the LCMN, was 16.5 mm. The average diameter of the MACN and the LCMN at their point of coaptation, were 2.7 mm and 3.5 mm, respectively. CONCLUSION: These nerve transfers are anatomically viable and could be a complement for other currently used techniques that can be employed in severely injured C567 brachial plexus patients.

Lobular Capillary Hemangioma of the External Jugular Vein: A Rare Case Report.

INTRODUCTION: Hemangiomas are benign tumors that are very common in the head and neck region. However, intravascular hemangiomas are very rare. Hemangiomas are classified as capillary, cavernous or mixed tumors according to the proliferating cells. Ultrasound, computed tomography, MR imaging and angiography are useful diagnostic tools and are generally required when planning surgical treatment. Definitive diagnosis is established by histopathological examination, differentiating hemangiomas from other vascular tumors or malignancies. CASE REPORT: We present a rare case of capillary hemangioma protruding from the external jugular vein. In our patient, the tumor was totally removed under local anesthesia. No complications and no recurrence were observed in the following two years. CONCLUSION: Intravascular tumors can present as neck masses and a definitive diagnosis is made by histopathological examination. Imaging tools provide important information about anatomy, the extent of the tumor, and for surgical planning.

CISH constrains the tuft-ILC2 circuit to set epithelial and immune tone.

Innate lymphoid cells (ILCs) are tissue-resident effectors poised to activate rapidly in response to local signals such as cytokines. To preserve homeostasis, ILCs must employ multiple pathways, including tonic suppressive mechanisms, to regulate their primed state and prevent inappropriate activation and immunopathology. Such mechanisms remain incompletely characterized. Here we show that cytokine-inducible SH2-containing protein (CISH), a suppressor of cytokine signaling (SOCS) family member, is highly and constitutively expressed in type 2 innate lymphoid cells (ILC2s). Mice that lack CISH either globally or conditionally in ILC2s show increased ILC2 expansion and activation, in association with reduced expression of genes inhibiting cell-cycle progression. Augmented proliferation and activation of CISH-deficient ILC2s increases basal and inflammation-induced numbers of intestinal tuft cells and accelerates clearance of the model helminth, Nippostrongylus brasiliensis, but compromises innate control of Salmonella typhimurium. Thus, CISH constrains ILC2 activity both tonically and after perturbation, and contributes to the regulation of immunity in mucosal tissue.

A role for IL-33-activated ILC2s in eosinophilic vasculitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare but serious disease with poorly understood mechanisms. Here, we report that patients with EGPA have elevated levels of TSLP, IL-25, and soluble ST2, which are well-characterized cytokine "alarmins" that activate or modulate type 2 innate lymphoid cells (ILC2s). Patients with active EGPA have a concurrent reduction in circulating ILC2s, suggesting a role for ILC2s in the pathogenesis of this disease. To explore the mechanism of these findings in patients, we established a model of EGPA in which active vasculitis and pulmonary hemorrhage were induced by IL-33 administration in predisposed, hypereosinophilic mice. In this model, induction of pulmonary hemorrhage and vasculitis was dependent on ILC2s and signaling through IL4Rα. In the absence of IL4Rα or STAT6, IL-33-treated mice had less vascular leak and pulmonary edema, less endothelial activation, and reduced eotaxin production, cumulatively leading to a reduction of pathologic eosinophil migration into the lung parenchyma. These results offer a mouse model for use in future mechanistic studies of EGPA, and they suggest that IL-33, ILC2s, and IL4Rα signaling may be potential targets for further study and therapeutic targeting in patients with EGPA.

Skin-resident innate lymphoid cells converge on a pathogenic effector state.

Tissue-resident innate lymphoid cells (ILCs) help sustain barrier function and respond to local signals. ILCs are traditionally classified as ILC1, ILC2 or ILC3 on the basis of their expression of specific transcription factors and cytokines1. In the skin, disease-specific production of ILC3-associated cytokines interleukin (IL)-17 and IL-22 in response to IL-23 signalling contributes to dermal inflammation in psoriasis. However, it is not known whether this response is initiated by pre-committed ILCs or by cell-state transitions. Here we show that the induction of psoriasis in mice by IL-23 or imiquimod reconfigures a spectrum of skin ILCs, which converge on a pathogenic ILC3-like state. Tissue-resident ILCs were necessary and sufficient, in the absence of circulatory ILCs, to drive pathology. Single-cell RNA-sequencing (scRNA-seq) profiles of skin ILCs along a time course of psoriatic inflammation formed a dense transcriptional continuum-even at steady state-reflecting fluid ILC states, including a naive or quiescent-like state and an ILC2 effector state. Upon disease induction, the continuum shifted rapidly to span a mixed, ILC3-like subset also expressing cytokines characteristic of ILC2s, which we inferred as arising through multiple trajectories. We confirmed the transition potential of quiescent-like and ILC2 states using in vitro experiments, single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) and in vivo fate mapping. Our results highlight the range and flexibility of skin ILC responses, suggesting that immune activities primed in healthy tissues dynamically adapt to provocations and, left unchecked, drive pathological remodelling.

Single-Cell Profiling Reveals Divergent, Globally Patterned Immune Responses in Murine Skin Inflammation.

Inflammatory response heterogeneity has impeded high-resolution dissection of diverse immune cell populations during activation. We characterize mouse cutaneous immune cells by single-cell RNA sequencing, after inducing inflammation using imiquimod and oxazolone dermatitis models. We identify 13 CD45+ subpopulations, which broadly represent most functionally characterized immune cell types. Oxazolone pervasively upregulates Jak2/Stat3 expression across T cells and antigen-presenting cells (APCs). Oxazolone also induces Il4/Il13 expression in newly infiltrating basophils, and Il4ra and Ccl24, most prominently in APCs. In contrast, imiquimod broadly upregulates Il17/Il22 and Ccl4/Ccl5. A comparative analysis of single-cell inflammatory transcriptional responses reveals that APC response to oxazolone is tightly restricted by cell identity, whereas imiquimod enforces shared programs on multiple APC populations in parallel. These global molecular patterns not only contrast immune responses on a systems level but also suggest that the mechanisms of new sources of inflammation can eventually be deduced by comparison to known signatures.