scholarly journals Case Report: Characterizing the Role of the STXBP2-R190C Monoallelic Mutation Found in a Patient With Hemophagocytic Syndrome and Langerhans Cell Histiocytosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura Viñas-Giménez ◽  
Rafael Rincón ◽  
Roger Colobran ◽  
Xavier de la Cruz ◽  
Verónica Paola Celis ◽  
...  
Keyword(s):  
Cell Line ◽  
Langerhans Cell Histiocytosis ◽  
Nk Cell ◽  
Adaptive Immune System ◽  
Langerhans Cell ◽  
Adaptive Immune ◽  
Life Threatening ◽  
Monoallelic Mutation ◽  
Nk Cell Cytotoxicity

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory disorder. HLH can be considered as a threshold disease depending on the trigger and the residual NK-cell cytotoxicity. In this study, we analyzed the molecular and functional impact of a novel monoallelic mutation found in a patient with two episodes of HLH. A 9-month-old child was diagnosed at 2 months of age with cutaneous Langerhans cell histiocytosis (LCH). After successful treatment, the patient developed an HLH episode. At 16 month of age, the patient went through an HSCT losing the engraftment 5 months later concomitant with an HLH relapse. The genetic study revealed a monoallelic mutation in the STXBP2 gene (.pArg190Cys). We transfected COS7 cells to analyze the STXBP2-R190C expression and to test the interaction with STX11. We used the RBL-2H3 cell line expressing STXBP2-WT-EGFP or R190C-EGFP for degranulation assays. Mutation STXBP2-R190C did not affect protein expression or interaction with syntaxin-11. However, we have demonstrated that STXBP2-R190C mutation diminishes degranulation in the RBL-2H3 cell line compared with the RBL-2H3 cell line transfected with STXBP2-WT or nontransfected. These results suggest that STXBP2-R190C mutation acts as a modifier of the degranulation process producing a decrease in degranulation. Therefore, under homeostatic conditions, the presence of one copy of STXBP2-R190 could generate sufficient degranulation capacity. However, it is likely that early in life when adaptive immune system functions are not sufficiently developed, an infection may not be resolved with this genetic background, leading to a hyperinflammation syndrome and eventually develop HLH. This analysis highlights the need for functional testing of new mutations to validate their role in genetic susceptibility and to establish the best possible treatment for these patients.

scholarly journals α-Pinene Enhances the Anticancer Activity of Natural Killer Cells via ERK/AKT Pathway

2021 ◽  
Vol 22 (2) ◽  
pp. 656
Author(s):  
Hantae Jo ◽  
Byungsun Cha ◽  
Haneul Kim ◽  
Sofia Brito ◽  
Byeong Mun Kwak ◽  
...  
Keyword(s):  
Nk Cells ◽  
Cancer Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Granzyme B ◽  
Akt Pathway ◽  
Cell Cytotoxicity ◽  
Anticancer Effects ◽  
Nk Cell Cytotoxicity

Natural killer (NK) cells are lymphocytes that can directly destroy cancer cells. When NK cells are activated, CD56 and CD107a markers are able to recognize cancer cells and release perforin and granzyme B proteins that induce apoptosis in the targeted cells. In this study, we focused on the role of phytoncides in activating NK cells and promoting anticancer effects. We tested the effects of several phytoncide compounds on NK-92mi cells and demonstrated that α-pinene treatment exhibited higher anticancer effects, as observed by the increased levels of perforin, granzyme B, CD56 and CD107a. Furthermore, α-pinene treatment in NK-92mi cells increased NK cell cytotoxicity in two different cell lines, and immunoblot assays revealed that the ERK/AKT pathway is involved in NK cell cytotoxicity in response to phytoncides. Furthermore, CT-26 colon cancer cells were allografted subcutaneously into BALB/c mice, and α-pinene treatment then inhibited allografted tumor growth. Our findings demonstrate that α-pinene activates NK cells and increases NK cell cytotoxicity, suggesting it is a potential compound for cancer immunotherapy.

A common pathway mediated through Toll-like receptors leads to T- and natural killer–cell immunosuppression

Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1437-1447 ◽  
Author(s):  
Ilan Vaknin ◽  
Liora Blinder ◽  
Lynn Wang ◽  
Roi Gazit ◽  
Elena Shapira ◽  
...  
Keyword(s):  
Natural Killer ◽  
Chronic Inflammation ◽  
Nk Cell ◽  
Killer Cell ◽  
Adaptive Immune System ◽  
Suppressor Cells ◽  
Toll Like Receptors ◽  
Down Regulation ◽  
Myeloid Suppressor Cells ◽  
Adaptive Immune

Abstract T- and natural killer (NK)–cell immunosuppression associated with ζ-chain down-regulation has been described in cancer, autoimmune, and infectious diseases. However, the precise stimuli leading to this bystander phenomenon in such different pathogen-dependent and sterile pathologies remained unresolved. Here, we demonstrate that Toll-like receptors (TLRs) play a major role in the induction of innate and adaptive immune system suppression; repetitive administration of single TLR 2, 3, 4, or 9 agonists, which do not exhibit any virulent or immune invasive properties, was sufficient to induce a bystander NK- and T-cell immunosuppression associated with ζ-chain down-regulation mediated by myeloid suppressor cells, as observed in the course of active pathologies. We identified a 35-amino acid (aa) region within the ζ-chain as being responsible for its degradation under TLR-mediated chronic inflammation. Furthermore, we provide evidence that ζ-chain levels could serve as a biomarker for chronic inflammation-dependent immunosuppression. Thus, although acute TLR-mediated activation could be beneficial in clearing pathogens or may serve as an immune adjuvant, such activation could be detrimental under sustained conditions.

scholarly journals Adult-Onset Langerhans Cell Histiocytosis And The Role of Vinblastine In The Treatment -Ankara Oncology Hospital Experience

2020 ◽  
Vol 53 (3) ◽  
pp. 492-499
Author(s):  
Ayşegül Tetik ◽  
Bahar Uncu Ulu ◽  
Mehmet Bakırtaş ◽  
Tuğçe Nur Yiğenoğlu ◽  
Jale Yıldız ◽  
...  
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Adult Onset ◽  
Hospital Experience

scholarly journals Adipocytes, Innate Immunity and Obesity: A Mini-Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Alecia M. Blaszczak ◽  
Anahita Jalilvand ◽  
Willa A. Hsueh
Keyword(s):  
Adipose Tissue ◽  
Immune System ◽  
Immune Cells ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Innate Immune Cells ◽  
Adaptive Immune

The role of adipose tissue (AT) inflammation in obesity and its multiple related-complications is a rapidly expanding area of scientific interest. Within the last 30 years, the role of the adipocyte as an endocrine and immunologic cell has been progressively established. Like the macrophage, the adipocyte is capable of linking the innate and adaptive immune system through the secretion of adipokines and cytokines; exosome release of lipids, hormones, and microRNAs; and contact interaction with other immune cells. Key innate immune cells in AT include adipocytes, macrophages, neutrophils, and innate lymphoid cells type 2 (ILC2s). The role of the innate immune system in promoting adipose tissue inflammation in obesity will be highlighted in this review. T cells and B cells also play important roles in contributing to AT inflammation and are discussed in this series in the chapter on adaptive immunity.

scholarly journals Childhood Langerhans cell histiocytosis with severe lung involvement: a nationwide cohort study

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Solenne Le Louet ◽  
Mohamed-Aziz Barkaoui ◽  
Jean Miron ◽  
Claire Galambrun ◽  
Nathalie Aladjidi ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Langerhans Cell Histiocytosis ◽  
Treatment Guidelines ◽  
Langerhans Cell ◽  
Infection Prophylaxis ◽  
Lung Involvement ◽  
Multisystem Disease ◽  
Abnormal Chest ◽  
Life Threatening ◽  
Severe Lung

Abstract Background Lung involvement in childhood Langerhans cell histiocytosis (LCH) is infrequent and rarely life threatening, but occasionally, severe presentations are observed. Methods Among 1482 children (< 15 years) registered in the French LCH registry (1994–2018), 111 (7.4%) had lung involvement. This retrospective study included data for 17 (1.1%) patients that required one or more intensive care unit (ICU) admissions for respiratory failure. Results The median age was 1.3 years at the first ICU hospitalization. Of the 17 patients, 14 presented with lung involvement at the LCH diagnosis, and 7 patients (41%) had concomitant involvement of risk-organ (hematologic, spleen, or liver). Thirty-five ICU hospitalizations were analysed. Among these, 22 (63%) were secondary to a pneumothorax, 5 (14%) were associated with important cystic lesions without pneumothorax, and 8 (23%) included a diffuse micronodular lung infiltration in the context of multisystem disease. First-line vinblastine–corticosteroid combination therapy was administered to 16 patients; 12 patients required a second-line therapy (cladribine: n = 7; etoposide-aracytine: n = 3; targeted therapy n = 2). A total of 6 children (35%) died (repeated pneumothorax: n = 3; diffuse micronodular lung infiltration in the context of multisystem disease: n = 2; following lung transplantation: n = 1). For survivors, the median follow-up after ICU was 11.2 years. Among these, 9 patients remain asymptomatic despite abnormal chest imaging. Conclusions Severe lung involvement is unusual in childhood LCH, but it is associated with high mortality. Treatment guidelines should be improved for this group of patients: viral infection prophylaxis and early administration of a new LCH therapy, such as targeted therapy.

Establishment of cell line and in vivo mouse model of canine Langerhans cell histiocytosis

2019 ◽  
Vol 17 (3) ◽  
pp. 345-353 ◽  
Author(s):  
Nguyen V. Son ◽  
Kazuyuki Uchida ◽  
Atigan Thongtharb ◽  
James K. Chambers ◽  
Takuya E. Kishimoto ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cell Line ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell

scholarly journals Langerhans cell histiocytosis: A case report with oral manifestations and the role of pediatric dentists in the diagnosis

2020 ◽  
Vol 8 (3) ◽  
pp. 545-549
Author(s):  
Eman Hussein Hammouri ◽  
Hala Antoun Sweidan ◽  
Omar AShokaibi ◽  
Leen Al Omari
Keyword(s):  
Case Report ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Oral Manifestations ◽  
Pediatric Dentists
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