BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease characterized by the accumulation of Langerhans cells within the lung tissue. The diagnosis of PLCH traditionally involves clinical, radiological, and lung biopsy histopathological evaluations.
METHODS: We present 2 cases where the diagnosis of PLCH was confirmed through the analysis of bronchoalveolar lavage (BAL) fluid cytology using immunoperoxidase technique, highlighting the significance of this minimally invasive technique in the diagnostic process. Clinical and radiological examination suggested advanced interstitial lung disease characterized by a fibrocystic pattern in both cases. The cytologic analysis of the BAL fluid revealed typical histiocytes with longitudinal grooves and eosinophils, which was better seen on liquid-based cytology (LBC) smears. ICC with CD1a, Langerin, and S-100 confirmed the diagnosis of PLCH.
CONCLUSIONS: Detecting PLCH through the examination of BAL cytology poses challenges, yet it is achievable, particularly with the assistance of LBC and ICC.

UNASSIGNED: The endocannabinoid system (ECS), named after the chemical compounds found in the cannabis plant, is a regulatory network of neurotransmitters, receptors, and enzymes that plays crucial roles in skin health and disease. Endogenous ligands of the ECS, called endocannabinoids, have proven to be important regulators of immune responses. One of the most prevalent endocannabinoids, arachidonoylethanolamide (also known as anandamide), is known for its anti-inflammatory effects. Langerhans cells (LCs) are the sole antigen-presenting cells present in the human epidermis. They serve as the first line of defense against pathogens and are essential for the skin\'s specific immune responses and play a critical role in maintaining tissue homeostasis; however, little is known about the effect of endocannabinoids on these cells. Our research aimed to provide the connection between monocyte-derived Langerhans cells (moLCs) and the ECS, shedding light on their collaborative roles in immune homeostasis and inflammation.
UNASSIGNED: Human monocytes were differentiated into moLCs using established protocols. Anandamide was applied during the differentiation process to test its effect on the viability, marker expression, and cytokine production of the cells, as well as in short term treatments for intracellular calcium measurement. TLR ligands applied after the differentiation protocol were used to activate moLCs. The impact of anandamide on the functionality of moLCs was further assessed using differential gene expression analysis of bulk RNA-Seq data, moLC-T cell cocultures, while ELISpot was employed to determine polarization of T cells activated in the aforementioned cocultures.
UNASSIGNED: Anandamide did not significantly affect the viability of moLCs up to 10 µM. When applied during the differentiation process it had only a negligible effect on CD207 expression, the prototypic marker of LCs; however, there was an observed reduction in CD1a expression by moLCs. Anandamide had no significant effects on the maturation status of moLCs, nor did it affect the maturation induced by TLR3 and TLR7/8 agonists. MoLCs differentiated in the presence of anandamide did however show decreased production of CXCL8, IL-6, IL-10 and IL-12 cytokines induced by TLR3 and TLR7/8 activation. Anandamide-treated moLCs showed an increased capability to activate naïve T cells; however, not to the level seen with combined TLR agonism. RNA sequencing analysis of moLCs differentiated with anandamide showed modest changes compared to control cells but did reveal an inhibitory effect on oxidative phosphorylation specifically in activated moLCs. Anandamide also promoted the polarization of naïve T cells towards a Th1 phenotype.
UNASSIGNED: Our results show that anandamide has nuanced effects on the differentiation, maturation, cytokine secretion, metabolism and function of activated moLCs. Among these changes the decrease in CD1a expression on moLCs holds promise to selectively dampen inflammation induced by CD1a restricted T cells, which have been implicated as drivers of inflammation in common inflammatory skin conditions such as psoriasis, atopic dermatitis and contact dermatitis.

The association among Langerhans cell histiocytosis, hematolymphoid malignancies, and heavy smoking has been addressed in medical literature to identify a possible potential link. Such occurrence can pose diagnostic challenges, as well as important clinical implications for disease progression and treatment approaches. We present pulmonary Langerhans cell histiocytosis instance in a 35-year-old male patient, with a 34-pack-year smoking history and nodular sclerosing Hodgkin lymphoma stage IIB who developed multiple bilateral lung nodules. The patient completed 6 cycles of doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine chemotherapy and radiotherapy 2 years earlier. CT chest scans revealed numerous micronodules scattered randomly throughout the upper and lower left lung lobes. Subsequent wedge resection exhibited cellular proliferation with grooved nuclei, eosinophilic cytoplasm, and surrounding inflammatory components. Immunohistochemical staining showed positive staining for S100 and CD1a confirming a diagnosis of pulmonary Langerhans cell histiocytosis. The patient responded to a 6-week treatment with vinblastine and prednisolone. A subsequent CT scan of the lungs revealed complete resolution after 3 years. This report underscores the importance of identifying pulmonary Langerhans cell histiocytosis in heavy smokers with Hodgkin lymphoma presenting with multiple nodular pulmonary lesions. For patients with Hodgkin lymphoma and a possible genetic predisposition, smoking may contribute to the overt development of pulmonary Langerhans cell histiocytosis. Therefore, smoking cessation and careful follow-up examinations are required. Further research is recommended to elucidate the underlying mechanisms of this intriguing association.

UNASSIGNED: The CD1A gene, a key component of the human immune system and part of the CD1 family, plays a crucial role in presenting lipid antigens to T cells. Abnormal CD1A expression is associated with various immune-related diseases and tumors. However, the biological function of CD1A in COAD is unclear.
UNASSIGNED: Multiple databases were systematically employed to conduct an analysis of CD1A expression in pan-cancer and COAD, along with its clinical-pathological features. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses of CD1A were performed using the \'clusterProfiler\' package. The Protein-protein interaction (PPI) analysis of CD1A was used the STRING database. Additionally, TIMER and ssGSEA tools were used to explore the relationship between CD1A expression in COAD and immune cell infiltration. The study also investigated the association between CD1A expression and N6-methyladenosine (m6A) modification genes in the TCGA COAD cohort and constructed a CD1A-centric competing endogenous RNA (ceRNA) regulatory network.
UNASSIGNED: CD1A displays varying expression levels in various tumors, including COAD, and is closely linked to clinical-pathological characteristics. GO analysis suggests that CD1A plays a role in important processes like antigen processing and presentation, leukocyte-mediated immunity, and lymphocyte-mediated immunity. KEGG analysis identifies CD1A\'s involvement in key pathways such as the Chemokine signaling pathway and Cytokine-cytokine receptor interaction. PPI analysis highlights CD1A\'s interactions with CD207, CD1C, CD1E, FOXP3, and ITGB2. ssGSEA analysis indicates a significant relationship between CD1A expression and the infiltration of various immune cells in COAD. Significant associations were found between CD1A and m6A modification genes in COAD. Furthermore, a CD1A-centered ceRNA regulatory network has been constructed.
UNASSIGNED: CD1A emerges as a potential biomarker for the diagnosis and treatment of COAD, showing a strong association with tumor immune infiltration, m6A modification, and the ceRNA network.

Exosome-enriched small extracellular vesicles (sEVs) are nanosized organelles known to participate in long distance communication between cells, including in the skin. Atopic dermatitis (AD) is a chronic inflammatory skin disease for which filaggrin (FLG) gene mutations are the strongest genetic risk factor. Filaggrin insufficiency affects multiple cellular function, but it is unclear if sEV-mediated cellular communication originating from the affected keratinocytes is also altered, and if this influences peptide and lipid antigen presentation to T cells in the skin.
Available mRNA and protein expression datasets from filaggrin-insufficient keratinocytes (shFLG), organotypic models and AD skin were used for gene ontology analysis with FunRich tool. sEVs secreted by shFLG and control shC cells were isolated from conditioned media by differential centrifugation. Mass spectrometry was carried out for lipidomic and proteomic profiling of the cells and sEVs. T cell responses to protein, peptide, CD1a lipid antigens, as well as phospholipase A2-digested or intact sEVs were measured by ELISpot and ELISA.
Data analysis revealed extensive remodeling of the sEV compartment in filaggrin insufficient keratinocytes, 3D models and the AD skin. Lipidomic profiles of shFLGsEV showed a reduction in the long chain (LCFAs) and polyunsaturated fatty acids (PUFAs; permissive CD1a ligands) and increased content of the bulky headgroup sphingolipids (non-permissive ligands). This resulted in a reduction of CD1a-mediated interferon-γ T cell responses to the lipids liberated from shFLG-generated sEVs in comparison to those induced by sEVs from control cells, and an increase in interleukin 13 secretion. The altered sEV lipidome reflected a generalized alteration in the cellular lipidome in filaggrin-insufficient cells and the skin of AD patients, resulting from a downregulation of key enzymes implicated in fatty acid elongation and desaturation, i.e., enzymes of the ACSL, ELOVL and FADS family.
We determined that sEVs constitute a source of antigens suitable for CD1a-mediated presentation to T cells. Lipids enclosed within the sEVs secreted on the background of filaggrin insufficiency contribute to allergic inflammation by reducing type 1 responses and inducing a type 2 bias from CD1a-restricted T cells, thus likely perpetuating allergic inflammation in the skin.

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Dendritic cells (DCs) are the most specialized antigen-presenting cells, and lymph nodes (LNs) play an important role in the DC-mediated T-cell response. We evaluated the infiltration of CD1a-positive DCs (CD1a-DCs), i.e., immature DCs, and S100-positive dendritic cells (S100-DCs), a mixture of immature and mature DCs, in 73 cases of laryngeal cancer and its regional LNs. Among them, 31 patients underwent radiotherapy (RT) or chemoradiotherapy (CRT) prior to surgery. No significant difference was found for CD1a-DC infiltration in the primary tumors, metastatic LNs and non-metastatic LNs, while S100-DCs were significantly fewer in number in the primary tumors and metastatic LNs compared to non-metastatic LNs. The cases which showed a high infiltration of S100-DCs in the metastatic LNs appeared to show a favorable prognosis, although statistical significance was not reached. In the RT/CRT group, the infiltration of the CD1a-DCs and S100-DCs was less in the primary tumors and metastatic LNs compared to the treatment-naive group. Conversely, the RT/CRT group showed higher CD1a-DC and S100-DC numbers in the non-metastatic LNs compared to the treatment-naïve group. Thus, DC maturation in metastatic LNs plays an important role in tumor immunity in laryngeal cancer, and the infiltration of DCs into the primary tumor and metastatic LNs is impaired by RT/CRT.

UNASSIGNED: Langerhans cells (LCs) are dendritic cells (DCs) of the epithelium which play a role in an array of oral lesions from gingivitis to oral cancer. Oral submucous fibrosis (OSMF), a potentially malignant disorder (PMD), is an insidious chronic disease with juxta-epithelial inflammatory changes leading to fibrosis. LCs may play a part in the ongoing inflammatory dysregulation of OSMF.
UNASSIGNED: The study was aimed at elucidating the distribution of LCs in varying grades of OSMF.
UNASSIGNED: A retrospective study using 18 cases of OSMF, graded using haematoxylin and eosin (H&E)-stained section. Immunohistochemistry was performed using polyclonal anti-CD1a antibodies to identify LCs in six cases of normal tissue and 18 samples of OSMF. The distribution of LCs among the various grades and normal mucosa analysed using Student\'s t-test.
UNASSIGNED: LC population in the OSMF was significantly higher when compared to the normal epithelium (p < 0.001). Within the grades, the advanced stage had more LCs than the other stages.
UNASSIGNED: The increase in LCs might indicate the role of antigenic exposure in turn leading to cell-mediated immunity in OSMF. Thus, the fibrosis in OSMF might have a direct link to LCs.

Oral cancer decreases quality of life despite timely medical management. The carcinogens in tobacco products and their role in tumorigenesis are well documented. Langerhans cells (LCs) are a subset of antigen-presenting cells (APCs) that monitor the tumor microenvironment and engulf carcinogens and foreign bodies. We investigated the distribution and size of LCs and their relation to the mode of tobacco consumption and clinical outcome in patients with buccal carcinoma. We recruited patients with oral cancer who were scheduled for tumor excision and men with urethral stricture undergoing substitution urethroplasty using buccal mucosa. Normal and tumor-adjacent tissues were stained with CD1a antibody. The distribution and mean diameter of 100 LCs/patient were determined. We found significantly smaller LCs in patients who chewed only tobacco compared to those who consumed tobacco by other means. The size of LCs decreased significantly with progressive stages of malignant disease. We found that patients with larger LCs survived longer than those with smaller LCs during an average follow-up of 24 months. We suggest a relation between the size of LCs and clinical outcomes in patients with buccal carcinoma.

Breast cancer (BC) is the most prevalent malignancy in women and researchers have strived to develop optimal strategies for its diagnosis and management. Neoadjuvant chemotherapy (NAC), which reduces tumor size, risk of metastasis and patient mortality, often also allows for a de-escalation of breast and axillary surgery. Nonetheless, complete pathological response (pCR) is achieved in no more than 40% of patients who underwent NAC. Dendritic cells (DCs) are professional antigen-presenting cells present in the tumor microenvironment. The multitude of their subtypes was shown to be associated with the pathological and clinical characteristics of BC, but it was not evaluated in BC tissue after NAC. We found that highe r densities of CD123+ plasmacytoid DCs (pDCs) were present in tumors that did not show pCR and had a higher residual cancer burden (RCB) score and class. They were of higher stage and grade and more frequently HER2-negative. The density of CD123+ pCDs was an independent predictor of pCR in the studied group. DC-LAMP+ mature DCs (mDCs) were also related to characteristics of clinical relevance (i.e., pCR, RCB, and nuclear grade), although no clear trends were identified. We conclude that CD123+ pDCs are candidates for a novel biomarker of BC response to NAC.