Abstract:
:The ability of cytotoxic lymphocytes (CL) to eliminate virus-infected or cancerous target cells through the granule exocytosis death pathway is critical to immune homeostasis. Congenital loss of CL function due to bi-allelic mutations in PRF1, UNC13D, STX11, or STXBP2 leads to a potentially fatal immune dysregulation, familial haemophagocytic lymphohistiocytosis (FHL). This occurs due to the failure of CLs to release functional pore-forming protein perforin and, therefore, inability to kill the target cell. Bi-allelic mutations in partner proteins STXBP2 or STX11 impair CL cytotoxicity due to failed docking/fusion of cytotoxic secretory granules with the plasma membrane. One unique feature of STXBP2- and STX11-deficient patient CLs is that their short-term in vitro treatment with a low concentration of IL-2 partially or completely restores natural killer (NK) cell degranulation and cytotoxicity, suggesting the existence of a secondary, yet unknown, pathway for secretory granule exocytosis. In the current report, we studied NK and T-cell function in an individual with late presentation of FHL due to hypomorphic bi-allelic mutations in STXBP2. Intriguingly, in addition to the expected alterations in the STXBP2 and STX11 proteins, we also observed a concomitant significant reduction in the expression of homologous STXBP1 protein and its partner STX1, which had never been implicated in CL function. Further analysis of human NK and T cells demonstrated a functional role for the STXBP1/STX1 axis in NK and CD8+ T-cell cytotoxicity, where it appears to be responsible for as much as 50% of their cytotoxic activity. This discovery suggests a unique and previously unappreciated interplay between STXBP/Munc proteins regulating the same essential granule exocytosis pathway.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Lopez JA,Noori T,Minson A,Li Jovanoska L,Thia K,Hildebrand MS,Akhlaghi H,Darcy PK,Kershaw MH,Brown NJ,Grigg A,Trapani JA,Voskoboinik Idoi
10.3389/fimmu.2018.00529subject
Has Abstractpub_date
2018-03-15 00:00:00pages
529issn
1664-3224journal_volume
9pub_type
杂志文章abstract::Genetic modification of mesenchymal stem cells (MSCs) is a promising strategy to improve their therapeutic effects. Granulocyte-colony stimulating factor (G-CSF) is a growth factor widely used in the clinical practice with known regenerative and immunomodulatory actions, including the mobilization of regulatory T cell...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01449
更新日期:2018-06-25 00:00:00
abstract::The composition of the oral milieu reflects oral health. Saliva provides an environment for multiple microorganisms, and contains soluble factors and immune cells. Neutrophils, which rapidly react on the changes in the microenvironment, are a major immune cell population in saliva and thus may serve as a biomarker for...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.565683
更新日期:2020-10-09 00:00:00
abstract::Elimination of potential self-reactive T cells in the thymus is crucial for preventing the onset of autoimmune diseases. Epithelial cell subsets localized in thymic medulla [medullary thymic epithelial cells (mTECs)] contribute to this process by supplying a wide range of self-antigens that are otherwise expressed in ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2013.00249
更新日期:2013-08-26 00:00:00
abstract::Interleukin-33 (IL-33) plays multiple roles in tissue homeostasis, prevention of parasitic infection, and induction of allergic inflammation. Especially, IL-33-ST2 (IL-1RL1) axis has been regarded as the villain in allergic diseases such as asthma and atopic dermatitis and in autoimmune diseases such as rheumatoid art...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02004
更新日期:2018-09-04 00:00:00
abstract::Although the role that Autoimmune Regulator (Aire) plays in the induction of central tolerance is well known, the precise cellular and molecular mechanisms are still unclear and debated. In the prevailing view, Aire serves mainly as a direct inducer of tissue-specific antigens. However, there is a growing amount of ev...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2013.00326
更新日期:2013-10-11 00:00:00
abstract::MicroRNAs (miRNAs) are a class of small, non-coding RNAs that are recognized as critical regulators of immune gene expression during infection. Many immunologically significant human miRNAs have been found to be conserved in agriculturally important species, including cattle. Discovering how bovine miRNAs mediate the ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2014.00611
更新日期:2014-11-27 00:00:00
abstract::Background: Infection with HIV-2, a retrovirus that is closely related to HIV-1, is characterized by slower disease progression and transmission, longer latency period and low or undetectable viremia. Host immunity, including production of potent neutralizing antibodies, may be one of the possible contributors to the ...
journal_title:Frontiers in immunology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.3389/fimmu.2018.02841
更新日期:2018-12-17 00:00:00
abstract::Macrophages form an important component of the innate immune system and serve as first responders against invading pathogens. While pathways critical for initiation of inflammatory responses between macrophages and other LysM+ myeloid cells are largely similar, it remains unknown whether a specific pathway has differe...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02882
更新日期:2018-12-06 00:00:00
abstract::The expression of human endogenous retroviruses (HERVs) has been associated with Multiple Sclerosis (MS). The MS-related retrovirus (MSRV/HERV-W) has the potential to activate inflammatory immunity, which could promote both susceptibility and progression toward MS. A connection between HERVs and MS is also supported b...
journal_title:Frontiers in immunology
pub_type: 临床试验,杂志文章
doi:10.3389/fimmu.2018.03092
更新日期:2019-01-22 00:00:00
abstract::Mucosal-associated Invariant T (MAIT) cells recognize vitamin B-based antigens presented by the non-polymorphic MHC class I related-1 molecule (MR1). Both MAIT T cell receptors (TCR) and MR1 are highly conserved among mammals, suggesting an important, and conserved, immune function. For many years, the antigens they r...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.01961
更新日期:2020-08-27 00:00:00
abstract::Immunological aging remodels the immune system at several levels. This has been documented in particular for the T-cell receptor (TCR)αβ+ T-cell compartment, showing reduced naive T-cell outputs and an accumulation of terminally differentiated clonally expanding effector T-cells, leading to increased proneness to auto...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00448
更新日期:2018-03-06 00:00:00
abstract::Natural killer (NK) cells are innate immune lymphocytes with potent cytolytic and immune-regulatory activities. NK cells are well-known for their ability to kill infected and malignant cells in a fast and non-specific way without prior sensitization. For this purpose, NK cells are equipped with a set of cytotoxic mole...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.03089
更新日期:2020-01-15 00:00:00
abstract::Myalgic encephalomyelitis (ME) often also called chronic fatigue syndrome (ME/CFS) is a common, debilitating, disease of unknown origin. Although a subject of controversy and a considerable scientific literature, we think that a solid understanding of ME/CFS pathogenesis is emerging. In this study, we compiled recent ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.00229
更新日期:2018-02-15 00:00:00
abstract::The small GTPase Rab5 is one of the master regulators of vesicular trafficking that participates in early stages of the endocytic pathway, such as endocytosis and endosome maturation. Three Rab5 isoforms (a, b, and c) share high sequence identity, and exhibit complex functions. However, the role of Rab5c in virus infe...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.02133
更新日期:2020-09-02 00:00:00
abstract::Plasminogen activation is essential for fibrinolysis-the breakdown of fibrin polymers in blood clots. Besides this important function, plasminogen activation participates in a wide variety of inflammatory conditions. One of these conditions is hereditary angioedema (HAE), a rare disease with characteristic attacks of ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.02046
更新日期:2019-08-27 00:00:00
abstract::Current pain therapeutics offer inadequate relief to patients with chronic pain. A growing literature supports that pro-inflammatory cytokine signaling between immune, glial, and neural cells is integral to the development of pathological pain. Modulation of these communications may hold the key to improved pain manag...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.03009
更新日期:2019-12-23 00:00:00
abstract:Purpose:Obesity is a major modifiable risk factor for cardiovascular disease. Bariatric surgery is considered to be the most effective treatment option for weight reduction in obese patients with and without type 2 diabetes (T2DM). Objective:To evaluate changes in lipoproteins, insulin resistance, mediators of systemi...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01512
更新日期:2017-11-15 00:00:00
abstract::Ischemic stroke is among the leading causes of disability and death worldwide. In acute ischemic stroke, the rapid recanalization of occluded cranial vessels is the primary therapeutic aim. However, experimental data (obtained using mostly the transient middle cerebral artery occlusion model) indicates that progressiv...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.02505
更新日期:2019-11-01 00:00:00
abstract::Chronic spontaneous urtcaria (CSU) can represent the leading sign of a wide spectrum of systemic diseases, including primary immunodeficiencies. We describe the case of a young adult female with coexisting CSU and common variable immunodeficiency (CVID) successfully treated with omalizumab. The patient, with a history...
journal_title:Frontiers in immunology
pub_type:
doi:10.3389/fimmu.2019.01700
更新日期:2019-07-17 00:00:00
abstract::M2 macrophage (Mφ) promotes pathologic angiogenesis through a release of pro-angiogenic mediators or the direct cell-cell interaction with endothelium in the micromilieu of several chronic inflammatory diseases, including rheumatoid arthritis and cancer, where interleukin (IL)-18 also contributes to excessive angiogen...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00334
更新日期:2018-03-06 00:00:00
abstract::Paneth cells contribute to intestinal innate immunity by sensing bacteria and secreting α-defensin. In Institute of Cancer Research (ICR) mice, α-defensin termed cryptdin (Crp) in Paneth cells consists of six major isoforms, Crp1 to 6. Despite accumulating evidences that α-defensin functions in controlling the intesti...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.570296
更新日期:2020-10-13 00:00:00
abstract::Single trauma injuries or isolated fractures are often manageable and generally heal without complications. In contrast, high-energy trauma results in multi/poly-trauma injury patterns presenting imbalanced pro- and anti- inflammatory responses often leading to immune dysfunction. These injuries often exhibit delayed ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.01056
更新日期:2020-06-04 00:00:00
abstract::Inflammation is a crucial defense mechanism that protects the body from the devastating effects of invading pathogens. However, an unrestrained inflammatory reaction may result in systemic manifestations with dire consequences to the host. The extent of activation of the inflammatory response is tightly regulated thro...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00551
更新日期:2018-03-19 00:00:00
abstract::Severe combined immunodeficiency (SCID) and other severe non-SCID primary immunodeficiencies (non-SCID PID) can be treated by allogeneic hematopoietic stem cell (HSC) transplantation, but when histocompatibility leukocyte antigen-matched donors are lacking, this can be a high-risk procedure. Correcting the patient's o...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2015.00250
更新日期:2015-05-21 00:00:00
abstract::Neuroinflammation in utero may result in lifelong neurological disabilities. Astrocytes play a pivotal role in this process, but the mechanisms are poorly understood. No early postnatal treatment strategies exist to enhance neuroprotective potential of astrocytes. We hypothesized that agonism on α7 nicotinic acetylcho...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01063
更新日期:2019-05-09 00:00:00
abstract::Follicular regulatory T cells (Tfr) are a unique subset of CD4 T cells that control and impact adaptive immune responses in the lymphoid follicles and germinal centers (GC). Since their relatively recent discovery, several studies have revealed that Tfr interact with other cells within this niche and shape ensuing res...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02704
更新日期:2018-11-20 00:00:00
abstract::The latest advancements in oncology research are focused on autologous immune cell therapy. However, the effectiveness of this type of immunotherapy for cancer remediation is not equivalent for all patients or cancer types. This suggests the need for better preclinical screening models that more closely recapitulate i...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00857
更新日期:2018-04-23 00:00:00
abstract::Bovine neonatal pancytopenia (BNP) was a vaccine-induced alloimmune disease observed in young calves and characterized by hemorrhages, pancytopenia, and severe destruction of the hematopoietic tissues. BNP was induced by alloreactive maternal antibodies present in the colostrum of certain cows vaccinated with a highly...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01902
更新日期:2018-08-14 00:00:00
abstract::[This corrects the article on p. 1376 in vol. 8, PMID: 29104576.]. ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,已发布勘误
doi:10.3389/fimmu.2017.01735
更新日期:2017-12-07 00:00:00
abstract::The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has generated a significant repercussion on the administration of adoptive cell therapies, including chimeric antigen receptor (CAR) T-cells. The closing of borders, the reduction of people transit and the confinement of the...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.573179
更新日期:2020-10-15 00:00:00