Eosinophilic Infiltration Research Articles

Ameliorative Potency of Iridoid Glucoside Compound Catalpol on Inhibiting NF-κB-mediated Inflammation in Allergic Rhinitis-induced Mice

Background Over time, the prevalence of allergic rhinitis (AR) has surged due to various risk factors, notably attributed to global urbanization, rendering heightened levels of pollutants, including traffic-related emissions and particulate matter. About 25% of the global children population and 40% of the adult population were reported with AR. Even though AR is recognized as a systemic inflammatory disease, it often results in diverse other comorbidities, such as dermatitis, sinusitis, conjunctivitis, and otitis, requiring extensive and expensive treatment. Purpose We assessed the effectiveness of iridoid glucoside catalpol against AR in a mouse model. Catalpol is recommended in traditional Chinese medicine to treat diverse acute and chronic diseases. Methods AR was induced in mice with an ovalbumin-sensitized AR model and treated with 10 and 20 mg of catalpol. Nasal severity scoring was performed to confirm the AR induction in mice. Allergic mediators immunoglobulin E (IgE) and histamine were quantified in the serum to assess the anti-allergic response of catalpol. In nasal lavage fluid (NALF), the inflammatory mediators IgE Ab, prostaglandin D2, leukotriene C4, eosinophil cationic protein (ECP), and pro-inflammatory cytokines were measured to analyze the anti-inflammatory potency of catalpol. The binding capacity of nuclear factor-kappa B (NF-κB) to DNA was evaluated to assess the catalpol inhibitory potency against NF-κB-mediated inflammation in AR mice. To confirm the ameliorative potency of catalpol in AR mice, a histopathological analysis of nasal mucosa was performed. Results Catalpol treatment significantly decreased the nasal symptoms and reduced the allergic mediators in the serum of experimental animals. It effectively inhibited the synthesis of inflammatory mediators, ECP, and pro-inflammatory cytokines in the NALF, and also suppressed the NF-κB DNA-binding activity in AR mice. The decrease in ciliary loss, goblet cells, eosinophil infiltration, and vascular congestion observed with our nasal mucosa histopathological analysis confirmed the ameliorative potency of catalpol. Conclusion Our findings have proven catalpol inhibits NF-κB-mediated inflammatory response in AR mice. With further analysis, a potent natural compound, catalpol, can be formulated as a drug to treat AR.

Squamous Cell Carcinoma with Prominent Eosinophils.

Eosinophils are often encountered in the stroma and peritumoral microenvironment of squamous cell carcinomas. Because eosinophils are readily identified on routine hematoxylin and eosin stained sections, researchers have explored multiple ways in which identifying the extent of eosinophil infiltration on routine biopsy and excisional specimens might provide diagnostic and prognostic information. We review the literature on this evolving topic.

Eosinophilic Dermatosis of Haematological Malignancy.

This report is regarding a 71-year-old female with a background of CLL diagnosed in 2017, managed conservatively with active surveillance under haematology. Presented to dermatology 5 years ago with a non-resolving insect bite-like rash on her chest. Multiple biopsies were taken over the years due to the diagnostic challenge. The biopsies usually demonstrated peri-vascular inflammation, heavy eosinophilic infiltrate along with lymphocytes and histiocytes without evidence of a frank vasculitis. Following multi-disciplinary team (MDT) discussion with clinical and pathological correlation, a diagnosis of eosinophilic dermatosis of haematological malignancy mimicking insect bites was made.

Shikonin alleviates asthma phenotypes in mice via an airway epithelial STAT3-dependent mechanism.

Asthma is an inflammatory disease where the balance between Th1/Th2 and Th17/Treg plays a crucial role in its pathogenesis. Shikonin is used to treat a variety of autoimmune diseases due to its good anti-inflammatory activity. However, the effect and mechanism of shikonin on asthma remain unknown. Mice were sensitized with ovalbumin (OVA)/house dust mite (HDM) and treated with shikonin. Lung inflammation was assessed histologically and via flow cytometry. Bronchoalveolar lavage fluid (BALF) was analyzed for cell counts and cytokines. Shikonin's impact on p-STAT3 was studied in vivo and in vitro. Shikonin inhibited OVA or HDM-induced inflammation and airway hyperresponsiveness. Upon treatment, a restoration of the Th1/Th2 and Th17/Treg balance was observed, evidenced by a reduction in IL-4 and IL-17A levels in BALF, alongside an elevation in interferon-gamma and IL-10. Furthermore, shikonin impeded the infiltration of eosinophils, neutrophils, macrophages, and lymphocytes into lung tissue. The observed decrease in STAT3 phosphorylation and diminished nuclear translocation of p-STAT3 confirmed that shikonin promotes the balance of Th1/Th2 and Th17/Treg by regulating airway epithelial STAT3. Shikonin mitigates asthma symptoms through a STAT3-dependent mechanism, indicating its potential as an anti-asthmatic therapeutic agent.

Antioxidative and Anti-Atopic Dermatitis Effects of Peptides Derived from Hydrolyzed Sebastes schlegelii Tail By-Products.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with significant morbidity, including pruritus, recurrent skin lesions, and immune dysregulation. This study aimed to investigate the antioxidative and anti-AD effects of peptides derived from hydrolyzed Sebastes schlegelii (Korea rockfish) tail by-products. Hydrolysates were prepared using various enzymes, including Alcalase, Flavourzyme, Neutrase, and Protamex. Among them, Protamex hydrolysates demonstrated the highest ABTS radical scavenging activity with an RC50 value of 69.69 ± 0.41 µg/mL. Peptides were further isolated from the Protamex hydrolysate using dialysis, fast protein liquid chromatography (FPLC), and high-performance liquid chromatography (HPLC). The most active peptide, STPO-B-II, exhibited a single peak and was identified as a sequence of Glu-Leu-Ala-Lys-Thr-Trp-His-Asp-Met-Lys, designated as MP003. In vivo experiments were conducted using a 2,4-dinitrochlorbenzene (DNCB)-induced AD model in NC/Nga mice. The isolated peptide, MP003, showed significantly reduced AD symptoms, including erythema, lichenification, and collagen deposition. Additionally, MP003 decreased epidermal and dermal thickness, eosinophil, and mast cell infiltration and downregulated the expression of pro-inflammatory cytokines IL-1β, IL-6, and IgE in serum and skin tissues. These findings suggest that peptides derived from Sebastes schlegelii tail by-products may serve as potential therapeutic agents for AD.

High-CBD Extract (CBD-X) in Asthma Management: Reducing Th2-Driven Cytokine Secretion and Neutrophil/Eosinophil Activity.

Asthma is a chronic inflammatory disorder of the airways affecting over 10% of the global population. It is characterized by airway inflammation, mucus hypersecretion, and bronchial hyperresponsiveness, driven predominantly by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s) in a subset of patients. However, a significant portion of asthmatic individuals present with "type 2-low" asthma that is often refractory to standard inhaled corticosteroid (ICS) therapy. Therefore, developing innovative therapeutic strategies has become essential. Recent studies have highlighted cannabidiol (CBD) as a promising anti-inflammatory agent capable of modulating immune responses. This study investigates the therapeutic potential of a high-CBD extract (CBD-X) in asthma. We evaluated the effects of CBD-X on cells involved in asthma pathogenesis using primary human Th2 cells, neutrophils, and asthma mouse model. Our findings indicate that CBD-X extract inhibits Th2 differentiation and reduces the secretion of IL-5 and IL-13, which are crucial cytokines in asthma. Additionally, CBD-X significantly reduces pro-inflammatory cytokines IL-8 and IL-6 in neutrophils and impairs their migration, a critical step in airway inflammation. In a murine asthma model, CBD-X administration led to marked downregulation of IgE and pro-asthmatic cytokines, along with reduced leukocyte, eosinophil, and neutrophil infiltration in lung tissues. These results suggest that CBD-X extract could offer a novel and complementary approach to managing both type 2-high and type 2-low asthma by targeting key inflammatory pathways and modulating immune cell behavior.

Eosinophilic esophagitis in children: a review of current guidelines based on case studies

Eosinophilic esophagitis (EoE) is still considered a rare disease. However, over the past decades, there has been an increase in publications on the diagnosis and treatment of EoE in both adults and children. Challenges in diagnosing EoE, especially in children, are associated with underestimation of risk factors and non-specific symptoms. For adults, the main symptom is dysphagia combined with eosinophilic infiltration of esophageal tissue (over 15 per field of view); thus, the diagnosis can be verified. The article presents a clinical case of EoE in an adolescent with an early atopic march and long-term retrosternal pain and dysphagia, and criteria for deciding on therapy are provided.

Kimura Disease: An Atypical Presentation

Abstract Introduction/Objective Kimura disease is a benign, chronic inflammatory process which presents with enlarged, painless lymphadenopathy. The etiology is currently unknown. It is most commonly seen in young males of Asian descent and is rare in other populations. It typically affects the subcutaneous tissue and regional lymph nodes, as well as the orbit and adnexal tissues. Clinically, peripheral eosinophilia and increased levels of immunoglobulin are commonly seen. Histologically, the disease presents with follicular hyperplasia with germinal center formation, hyperplastic vasculature, increased eosinophilic inflammatory infiltrate, and characteristic Warthin-Finkedly cells. Methods/Case Report A 70-year-old white male with no significant past medical history presented to an outpatient clinic with a painless right eyebrow mass. The mass had grown in size which prompted the patient to seek evaluation. The decision to excise the mass was made. Upon pathologic review, hematological workup was performed, and the case was subsequently diagnosed as Kimura disease. Results (if a Case Study enter NA) The specimen was excised and H&E showed background benign fibroadipose tissue with prominent, lymphoid follicles. Within the follicles, there was a significant increase in eosinophils. Warthin- Finkeldey cells were commonly identified within germinal centers as well. Immunohistochemical staining was performed with appropriate controls which ruled out other common lymphoid malignancies and to the diagnosis of Kimura Disease. Conclusion Kimura disease is a rare, benign inflammatory disorder that most commonly affects the lymph nodes. It may be overlooked histologically when the patient does not fit the typical clinical picture. It can closely resemble neoplastic, hematologic conditions, and it should be distinguished from a more aggressive entity due to its benign, indolent behavior. From a pathologist’s point of view, because it occurs almost exclusively in young, Asian males, it is important to consider when presented with an atypical demographic to avoid unnecessary additional workup.

Eosinophilic gastroenteritis, a rare case report and literature review

Abstract Introduction/Objective Eosinophilic gastroenteritis (EGE) is a rare inflammatory condition affecting the gastrointestinal tract, initially described by Kaijser et al. in 1937. It manifests as eosinophil-rich infiltration throughout the GI tract, often accompanied by peripheral eosinophilia. EGE is categorized under eosinophilic gastrointestinal disorders (EGIDs), alongside eosinophilic esophagitis (EOE) and eosinophilic colitis (EC). Symptoms vary based on the affected GI segment. This report aims to present a case of extensive EGE in a young male patient and review of similar cases to enhance clinical and histopathologic understanding. Methods/Case Report A 29-year-old male presented with abdominal pain, nausea, vomiting, and recent weight loss. He had a history of similar abdominal symptoms for a few years. Previous extensive investigations were inconclusive. Current imaging revealed soft tissue nodules, mild splenomegaly, and biliary dilation. Laboratory tests showed no significant abnormalities. Endoscopy revealed a gastric antral ulcer with marked eosinophilic infiltration on microscopy. Results (if a Case Study enter NA) NA Conclusion Eosinophilic gastroenteritis is an uncommon disease that presents with variable non-specific symptoms which require a high level of suspicion for diagnosis. EGE diagnosis requires excluding other causes of eosinophil accumulation. There is no clear distinction between the upper normal and abnormally increased eosinophils in GIT biopsies. Peripheral eosinophilia is common, along with other abnormal laboratory findings. Diagnosis relies on histopathology due to nonspecific symptoms. Clinicians and pathologists face challenges in diagnosing EGE, emphasizing the importance of considering it in the differential diagnoses. Efforts to establish diagnostic criteria for EGE are limited, despite its long-known existence. The condition’s vague symptoms necessitate a high level of clinical suspicion, with diagnosis primarily based on histopathologic features.

Urogenital schistosomiasis, a leading cause of bladder squamous cell carcinoma

Abstract Introduction/Objective Schistosoma, genus of trematodes, commonly known as blood flukes are parasitic flatworms responsible for a group of infections in humans termed schistosomiasis and hundreds of millions of people are infected worldwide. In areas where Shistosoma is not endemic to the region most cases of bladder malignancy are of urothelial origin. In areas where Shistosoma is endemic bladder malignancy is more commonly squamous cell carcinoma. However, with increased travel, migration and tourism it is important to potentially consider Shistosoma infection in areas that are not typically considered endemic regions. Methods/Case Report A 62-year-old male presented to our hospital and revealed through an interpreter he has had 1.5 years hematuria with “pieces of meat or brown dirt”. Cystoscopy was performed and showed a large necrotic mass. CT scan showed an 8.2 cm exophytic bladder dome mass. TURBT was performed and a diagnosis of invasive high-grade urothelial carcinoma with squamous differentiation and with multiple Schistosoma organisms identified.The patient received Schistosoma treatment and was scheduled for radical cystectomy and ileal conduct. A few days before the scheduled procedure the patient presented to our emergency department with acute abdominal pain. He was subsequently diagnosed with progressive bladder cancer with new left malignant ureteral obstruction, which lead to hydronephrosis, DVT, abdominopelvic ascites and intraperitoneal bladder perforation. Abdominal fluid cytology showed atypical keratinizing squamous cells suspicous for malignancy and marked acute inflammation. Patient underwent cystectomy with ileal conduit and the specimen was sent to pathology for examination. Results (if a Case Study enter NA) NA Conclusion Gross examination showed an irregular perforated bladder. Microscopic examination showed a high grade urothelial carcinoma with squamous and sarcomatoid differentiation with detrusor muscle invasion. Additionally, Schistosoma organisms with a terminal spine and calcified eggs were identified. Some of the calcified egg material was engulfed by giant cells. The organisms are surrounded by a prominent eosinophilic infiltrate. Lymphovascular invasion is also noted. Schistosomiasis is associated with the development of squamous cell carcinoma of the bladder. It is important to maintain high oncological alertness for squamous cell carcinoma, particularly for patients arriving from endemic areas. Such as in our case, a patient from Somalia living in Kansas City.

Recombinant RSV G protein vaccine induces enhanced respiratory disease via IL-13 and mucin overproduction

The G protein expressed on the surface of respiratory syncytial virus (RSV) is important for adhesion to host cells and as a vaccine target antigen. The corresponding vaccines can effectively eliminate RSV. However, they exacerbate pulmonary immunopathology including eosinophilic infiltration in the lungs after an RSV challenge in animal models, raising concerns about enhanced respiratory disease (ERD); thus, approaches that mitigate these effects are urgently needed. Herein, we aimed to examine the mechanisms of G protein vaccine-induced ERD in mice, using recombinant G protein as a vaccine antigen. After the RSV challenge, G protein-vaccinated mice exhibited lung weight gain, lung tissue damage, and increased infiltration of eosinophils, neutrophils, and CD4+ T cells into the lungs. We set lung weight gain as the endpoint for ERD and examined the impact of each infiltrating cell on lung weight gain. We observed that CD4+ T cells, but not eosinophils or neutrophils, that infiltrate the lungs are responsible for lung weight gain. In addition, T helper 2 cell-mediated IL-13 induced mucin hypersecretion and lung weight gain. Mucin hypersecretion may contribute to weight gain in the lungs. In conclusion, our results indicate a novel mechanism of G protein vaccine-induced ERD via IL-13 and mucin hypersecretion, which could lead to the development of safe G protein vaccines and the elucidation of the causes of ERD associated with other vaccines.

Prurigo chronica multiformis: Expert consensus of the Japanese Dermatological Association.

Prurigo chronica multiformis is a commonly used diagnostic designation for a peculiar subtype of prurigo in Japan, although the disease entity might not be well-recognized in other countries. Experts approved by the Japanese Dermatological Association attempted to build a common consensus on prurigo chronica multiformis, agreeing that it is a unique and important disease entity in elderly patients. Skin lesions are characterized by intensely pruritic, edematous, urticarial papules, or small macules, which gradually become solid papules/small nodules. The papules tend to aggregate and occasionally coalesce into polygonal lichenified plaques. The most commonly affected sites are the lower abdomen and lower back, although the chest, thighs, and upper back might also be involved. Common histopathological features of prurigo chronica multiformis include infiltration of lymphocytes and eosinophils in the upper dermis, with minimal epidermal changes. Basophil infiltration is also observed. The epidemiological incidence, differences in clinical manifestations by geographical location, and disease placement among other forms of prurigo and/or related skin diseases need to be further elucidated. Dermatologists should be aware of the clinical characteristics of prurigo chronica multiformis.

High M2/M1 Macrophage Ratio Observed in Nasal Polyps Formed in Allergic Fungal Rhinosinusitis.

Allergic fungal rhinosinusitis (AFRS) shares similarities with eosinophilic chronic rhinosinusitis (ECRS), both characterized by intractable nasal polyps. The key distinction lies in the presence of fungal infection within the nasal cavity. While ECRS nasal polyps are known for significant infiltration of M2 macrophages and eosinophils, as well as an increase in high endothelial venule (HEV)-like vessels, these features are less commonly reported in AFRS. This study compared clinicopathological findings between AFRS (n=10), ECRS (n=12), and non-ECRS (n=10) patients' nasal polyps using immunohistochemical analysis for CD163 and CD68 to assess the M2/M1 macrophage ratio, and peripheral lymph node addressin (PNAd) and CD34 to evaluate the proportion of HEV-like vessels. AFRS showed a significantly higher number of CD163-positive M2 macrophages and an increased M2/M1 ratio compared with ECRS. However, the percentage of HEV-like vessels and the number of eosinophils infiltrating the nasal polyps were similar in both AFRS and ECRS. The observed increase in M2 macrophages in AFRS nasal polyps is presumed to be induced by fungal infection in the nasal cavity, in comparison with ECRS. These results highlight the distinctive immunological profiles of AFRS and ECRS, emphasizing the role of macrophage polarization in their pathogenesis.

The therapeutic effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol on chemically induced atopic dermatitis

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease worldwide. However, it is still urgent to develop innovative treatments that can effectively manage refractory patients with unpredictable chronic disease courses. In this study, we evaluated the therapeutic efficacy of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) as a novel agent for AD treatment using a human-like mouse model of AD. PLAG significantly improved 2,4-dinitrochlorobenzene (DNCB)-induced AD skin lesions compared to those in mice treated with DNCB alone. PLAG substantially modulated the AD-induced infiltration of monocytes and eosinophils into skin lesions and humoral systemic responses involving immunoglobulin E (IgE), interleukin (IL)-4, and IL-13, restoring them to a normal state. Next, we compared the therapeutic efficacy of PLAG and abrocitinib for severe AD treatment. PLAG exhibited a significant therapeutic effect on AD skin lesions compared to abrocitinib. Unlike abrocitinib, PLAG significantly reduced AD-induced eosinophil infiltration to a level similar to that observed in untreated negative controls. Notably, both PLAG and abrocitinib downregulated IgE, IL-4, and IL-13 in a similar pattern, reaching levels similar to those in the untreated negative controls. Our findings strongly suggest that PLAG may serve as a therapeutic agent for AD with an efficacy comparable to that of abrocitinib.

8110 Lymphocytic Hypophysitis secondary to a ruptured Rathke’s Cleft Cyst complicated by post surgical recurrence: A rare phenomenon

Abstract Disclosure: M.S. Maharaul: None. F. Thelmo: None. I. Ahmed: None. Introduction: Lymphocytic hypophysitis secondary to ruptured Rathke’s cleft cyst (RCC) is a rare entity. Rathke’s cleft cysts are benign fluid-filled intra-sellar cysts that originate from the remnants of Rathke’s pouch and contain mucoid material. Most are asymptomatic; some may get symptomatic during cyst expansion and rupture releasing liquid content and trigger local inflammation. Surgical resection followed by glucocorticoids is usually curative. Case: A 42-year-old female presented to the hospital with one week history of right sided frontal headache associated with blurred vision in right eye. MRI Brain showed a 15 mm complex cystic lesion in the sella with suprasellar extension associated with peripheral calcifications. On admission, endocrine laboratory investigations including pregnancy test were normal. Ophthalmic testing did not reveal any acute abnormalities. Transsphenoidal surgery was performed for tumor resection. Pathology examination revealed infiltration of massive lymphocytes, macrophages, plasma cells, and eosinophils that were diagnostic of lymphocytic hypophysitis in the anterior pituitary lobe. She was started on glucocorticoids and discharged home. Rheumatology and Infectious diseases workup were unrevealing. On follow up 3 weeks later, she had self-discontinued steroids. The following week, she presented to the emergency room again with a right sided headache and blurred vision. MRI Brain revealed a 16 mm recurrent inflammatory mass lesion in the sella. Endocrine panel demonstrated an 8 am serum cortisol level of 7.4 mcg/dl, ACTH 20 pg/ml, FSH 6.2 mIU/ml, LH 4.9 mIU/ml, free T4 1.1 ng/dl and prolactin 8 ng/ml. She underwent transsphenoidal resection of the mass again and was restarted on glucocorticoids. This time pathology examination revealed an epithelial lined cyst most compatible with Rathke’s cleft cyst. She continued to remain on a glucocorticoid taper during the follow up period. On re-evaluation, her endocrinology laboratory investigations continued to show a deficiency of gonadotropins for which she is following up with OBGYN, but the remaining pituitary hormones were all within normal limits. Conclusion: Rathke’s Cleft Cysts (RCCs) should be in the differential diagnoses for evaluation of hypophysitis. There have only been a handful of cases in the literature of hypophysitis associated with a ruptured RCC, and only one case of recurrence after surgical debulking. This case provides an insight into the clinical behavior, diagnosis, and timely management of lymphocytic hypophysitis due to a ruptured Rathke’s cleft cyst and management post-recurrence. Presentation: 6/3/2024

Preclinical Models of Atopic Dermatitis Suitable for Mechanistic and Therapeutic Investigations.

Atopic dermatitis (AD) is a complex immune-mediated abnormality of the skin characterized by impaired barrier function, eczematous dermatitis, chronic pruritus and itch. The immunological response in AD is mediated by a Th2-dominated immune response in the early acute phase followed by a Th1/ Th2 mixed immune response in the chronic phase. AD is the first step of the "atopic march" that progresses into food allergy, allergic rhinitis, and asthma. Different models are indispensable for studying AD pathogenesis and for designing pre-clinical studies for therapeutic discovery. They reflect the characteristic morphological features of typical human AD with regard to epidermal thickening, hyperkeratosis, acanthosis, and spongiosis and help understand the immunopathogenesis of the disease with respect to IgE levels and cellular infiltration of eosinophils, mast cells, and lymphocytes. Although it is difficult to replicate all human AD clinical features in a model, several AD in vivo models comprising spontaneous, induced, transgenic, and humanized and in vitro models, including 2D, co-culture, and 3D, have been described previously. However, several questions remain regarding whether these models satisfactorily reflect the complexity of human AD. Therefore, this review comprehensively highlights the diversity of currently available models and provides insights into the selection of suitable models based on research questions. It also summarizes the diverse mechanisms associated with each model, which may be valuable for better study design to test new therapeutic options.

Eosinophilic esophagitis (EoE) in adults in Icelandic and international context

Eosinophilic esophagitis (EoE) is a common cause of swallowing difficulties in both children and adults. The incidence of EoE has been increasing over the past decades, which cannot be solely attributed to improved diagnostic techniques. EoE is more common in adults than in children. The diagnosis is confirmed by a biopsy from the esophageal mucosa showing a significant infiltration of eosinophils. Many patients respond to treatment with proton pump inhibitors, but those with severe EoE may require dietary modifications, topical steroids, and/or dilation of esophageal strictures. This review covers the incidence, risk factors, natural course, diagnosis, and treatment options for EoE, both within the Icelandic healthcare system andi n a broader context.

A case of chronic spontaneous urticaria with wheals lasting for more than a week.

Urticaria is characterized by the development of wheals which usually disappear within a day, and are not present beyond a few days. A 58-year-old man began to develop edematous, partially ring-shaped erythematous lesions accompanied by severe body itching without any particular cause, approximately 2 months before his first visit to our hospital. Each rash emerged as being about 5 mm in diameter, gradually enlarging over several days, and disappeared in up to 10 days. Despite oral treatment with several antihistamines and 10 mg of prednisolone, there was no improvement. Most eruptions disappeared without a trace, but the erythema that appeared on the palms left desquamation. The patient had a history of shellfish allergy, but otherwise no atopic diseases. Drug eruption was ruled out due to a lack of regular taking other medications. Histopathological findings of the skin lesions showed moderate lymphocytic and few eosinophilic infiltrates with edema, but no evidence of vasculitis. Despite the concomitant use of two second-generation antihistamines and montelukast, the rash did not improve. The symptoms began to improve following oral intake of 1.5 mg of betamethasone, which was tapered off with the addition of 150 mg of cyclosporin. The use of all medications was stopped at 4 months from the first visit without recurrence. Wheals of chronic spontaneous urticaria may last for longer than a week without apparent histopathological findings of vasculitis.

CD226 implicated in Akt-dependent apoptosis of CD4+ T cell contributes to asthmatic pathogenesis.

Asthma is a chronic airway inflammatory disease in which CD4+ T cell dysregulation occurs. Here, we investigated the molecular role and clinical significance of CD226, a costimulatory molecule of T lymphocytes, in the development of allergic asthma. Our results revealed that the expression of CD226 was significantly increased in CD4+ effector T cells, especially in T helper (Th) 2 cells and Th17 cells in patients with asthma. Moreover, CD4+ T cell-specific Cd226-knockout mice were generated and together with littermates were challenged with ovalbumin (OVA) to establish a model of allergic asthma. We found that CD226 deficiency in CD4+ T cells mitigated lung inflammation, IgE production, and eosinophil infiltration and reduced airway remodeling in experimental allergic asthma. However, the impact of CD226 on asthma was independent of Treg cell modulation. Through RNA-seq data analysis, the apoptosis pathway was screened. Mechanistically, CD226 deletion promoted CD4+ T cell late apoptosis via the activation of Caspase-3 in an Akt-dependent manner. Furthermore, blocking CD226 signaling with a recombinant fusion protein attenuated asthma features in mice and achieved a good therapeutic effect. Overall, this study revealed a unique role of CD226 in CD4+ T cell regulation in asthma pathogenesis. Therefore, targeting CD226 may provide new insights into the clinical treatment of asthma.

Postnatal Allergic Inhalation Induces Glial Inflammation in the Olfactory Bulb and Leads to Autism-Like Traits in Mice

Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders. To explore its pathophysiology, we investigated the association between neonatal allergic exposure and behavioral changes. Adult female C57BL/6J mice were immunized with adjuvant (aluminum hydroxide) or ovalbumin emulsified with adjuvant. After immunization, the mice were mated, and offspring were born at full term. The postnatal dams and infants were then simultaneously exposed to an allergen (ovalbumin) or vehicle via inhalation. After weaning, behavioral testing and histopathological analyses were conducted on male offspring. Compared with the vehicle-exposed offspring, the ovalbumin-exposed offspring had decreased sociability and increased repetitive behavior, thus representing an ASD-like phenotype in mice. Moreover, histopathological analyses revealed that the ovalbumin-exposed mice had increased astroglial, microglial, and eosinophilic infiltration in the olfactory bulb, as well as increased eosinophils in the nasal mucosa. The ovalbumin-exposed mice also had decreased dendritic spine density and a lower proportion of mature spines, suggesting the impairment of stimulus-induced synaptogenesis. In conclusion, postnatal allergic exposure induced an ASD-like phenotype, as well as allergic rhinitis, which was followed by glial inflammation in the olfactory bulb parenchyma.