Clinical and Experimental Immunology

Recombination activating genes (RAG) 1/2 deficiency leads to combined T/B cell deficiency with varying clinical presentations. This study aimed to define the clinical/laboratory spectrum of RAG1/2 deficiency. We retrospectively reviewed the clinical/laboratory data of 35 patients, grouped them as severe combined immunodeficiency (SCID), Omenn Syndrome (OS), and delayed-onset combined immunodeficiency (CID) and reported nine novel mutations. Male/female ratio was 23/12. Median age of clinical manifestations was 1 months (mo) (0...

Interleukin-11 is a cytokine from the IL-6 family of cytokines that includes IL-6 and OSM. Initially described for its role in platelet generation, it is now appreciated that this cytokine has multiple functions. Recently it has been found that IL-11 is critical in fibrosis in multiple different organ systems and systemically as in the autoimmune disease systemic sclerosis. Animal models of fibrosis have determined that animals with IL-11 receptor deletions have retarded fibrosis and that in wild type animals IL-11 is found at the organ of fibrosis...

The overlapping of two or more types of neural autoantibodies in one patient has increasingly been documented in recent years. The coexistence of myelin oligodendrocyte glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) antibodies is most common, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis, clinical manifestations, paraclinical features, and treatment of MNOS. Forty-nine patients with MNOS were included in this study...

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease caused by intrahepatic bile duct injuries, resulting in fibrosis, cirrhosis, and eventually liver failure. T helper (Th) 17 cells are proposed to involve in the pathogenesis of PBC. However, how and which Th17 cell-derived cytokines affect PBC remains unclear. In this study, we investigated the effects of Th17 effector cytokines, including interleukin (IL)-17A, IL-17F, and IL-21 in PBC using a xenobiotic-induced mouse model of autoimmune cholangitis (inducible chemical xenobiotic models of PBC) treated with cytokine-expressing adeno-associated virus...

Chemo-immunotherapy has become the best first-line treatment for advanced lung cancer patients without oncogenic drivers. However, it may also lead to an increased incidence and severity of treatment-related adverse events. In this retrospective study, lung cancer patients administrated with either anti-PD-1 or anti-PD-L1 treatment plus chemotherapy were included. Data on demographic characteristics, disease characteristics, treatment strategies, laboratory results and clinical outcomes were collected from the Electronic Medical Records System and evaluation scales...

The excessive formation of neutrophil extracellular traps (NETs) has been demonstrated to be a pathogenic mechanism of idiopathic inflammatory myopathy (IIM)-associated interstitial lung disease (ILD). This study aimed to answer whether an experimental autoimmune myositis (EAM) model can be used to study IIM-ILD and whether NETs participate in the development of EAM-ILD. An EAM mouse model was established using skeletal muscle homogenate and pertussis toxin (PTX). The relationship between NETs and the ILD phenotype was determined via histopathological analysis...

OBJECTIVE: To evaluate the relationship between immunological markers and clinical outcome measures in a mixed cohort of patients with typical CIDP and CIDP variants at different disease stages. METHODS: Twenty-three typical, 16 multifocal and 5 distal CIDP patients were included. Twenty-five sex and age-matched healthy controls and 12 patients with Charcot-Marie-Tooth type 1A (CMT1A) disease served as controls. Peripheral B-cell populations were analyzed by flow cytometry...

Due to the aggravation of bacterial drug resistance and the lag in the development of new antibiotics, it is crucial to develop novel therapeutic regimens for bacterial infectious diseases. Currently, immunotherapy is a promising regimen for the treatment of infectious diseases. Mucosal-associated invariant T (MAIT) cells, a subpopulation of innate-like T cells, are abundant in humans and can mount a rapid immune response to pathogens, thus becoming a potential target of immunotherapy for infectious diseases...

A sex disparity in asthma prevalence and severity exists in humans. Multiple studies have highlighted the role for innate cells in shaping the adaptive immune system in chronic asthma. To explore the sex bias in the eosinophilic response, we delivered IL-33 to the lungs of mice and delineated the kinetics by which the inflammatory response was induced. Our data demonstrate that females recruited more eosinophils capable of responding to IL-33. Eosinophil activation occurred selectively in the lung tissue and was enhanced in females at all time points...

Respiratory syncytial virus (RSV) infections are a major cause of bronchiolitis and pneumonia in infants and older adults, for which there is no known correlate of protection. Increasing evidence suggests that Fc-mediated antibody effector functions have an important role, but little is known about the development, heterogeneity, and durability of these functional responses. In light of future vaccine strategies, a clear view of the immunological background and differences between various target populations is of crucial importance...

NOD-like receptor family, pyrin domain-containing 3 (NLRP3) is a central protein contributing to human inflammatory disorders, including cryopyrin associated periodic syndrome and sepsis. However, the molecular mechanisms and functions of NLRP3 activation in various diseases remain unknow. Here, we generated gain-of-function knock-in mice associated with Muckle-Wells syndromes using the Cre-LoxP system allowing for the constitutive T346M mutation of NLRP3 to be globally expressed in all cells under the control of tamoxifen...

Airway remodeling is a major feature of asthma. Interleukin (IL)-36γ is significantly up-regulated and promotes airway hyperresponsiveness (AHR) in asthma, but its role in airway remodeling is unknown. Here, we aimed to investigate the role of IL-36γ in airway remodeling, and whether IL-38 can alleviate airway remodeling in chronic asthma by blocking the effects of IL-36γ. IL-36γ was quantified in mice inhaled with house dust mite (HDM). Extracellular matrix (ECM) deposition in lung tissues and AHR were assessed following IL-36γ administration to mice...

Crohn's disease (CD) is a chronic immune-mediated disorder of the gastrointestinal tract. Extensive screening studies have revealed the accumulation of immune cell subsets with unique plasticity and immunoregulatory properties in patients with CD. We performed phenotypic and functional studies on inflamed and non-inflamed bioptic tissue to investigate the presence of distinct T cells in the intestinal mucosa of CD patients. We analyzed hundreds of surface molecules expressed on cells isolated from the intestinal tissue of CD patients using anti-CD45 mAbs-based barcoding...

Mounting evidence has indicated the essential role of tissue-resident memory T (TRM) cells for frontline protection against viral infection and for cancer immune surveillance 1. TRM cells are transcriptionally, phenotypically, and functionally distinct from circulating memory T (Tcirm) cells. It is necessary to understand the unique ontogenetic mechanism, migratory regulation, and biological function of TRM cells. In this review, we discuss recent insights into cellular mechanisms and discrete responsiveness in different tissue microenvironments underlying TRM cell development...

Innate immune activity fuels intestinal inflammation in Crohn's disease (CD), an inflammatory bowel disease (IBD). Identification and targeting of new molecular regulators of the innate activity are warranted to control the disease. Inhibitor of apoptosis proteins (IAPs) regulate both cell survival and inflammatory signaling. We investigated effects of IAP inhibition by second mitochondria-derived activator of caspases (SMAC) mimetics (SMs) on innate responses and cell death to pathogen-associated molecular patterns in peripheral blood mononuclear cells (PBMCs) and monocytes...

Staphylococcus aureus (SA) and its exotoxins activate eosinophils (Eos) and mast cells (MCs) via CD48, a GPI-anchored receptor belonging to the Signaling Lymphocytes Activation Molecules (SLAM) family. 2B4 (CD244), an immuno-regulatory transmembrane receptor also belonging to the SLAM family, is the high affinity ligand for CD48. 2B4 is expressed on several leukocytes including NK cells, T cells, basophils, monocytes, dendritic cells (DCs) and Eos. In the Eos and MCs crosstalk carried out by physical and soluble interactions (named the 'Allergic Effector Unit', AEU), 2B4-CD48 binding plays a central role...

Primary adrenal insufficiency (PAI) is most often caused by an autoimmune destruction of the adrenal cortex resulting in failure to produce cortisol and aldosterone. The aetiology is thought to be a combination of genetic and environmental risk factors, leading to breakdown of immunological tolerance. Regulatory T cells (Tregs) are deficient in many autoimmune disorders, but it is not known whether they contribute to development of PAI. We aimed to investigate the frequency and function of naïve and expanded Tregs from patients with PAI and polyendocrine syndromes compared to age- and gender-matched healthy controls...

The mucosal immune system is implicated in the etiology and progression of inflammatory bowel diseases. The lamina propria and epithelium of the gut mucosa constitute two separate compartments, containing distinct T cell populations. Human CD4 T cell programming and regulation of lamina propria and epithelium CD4 T cells, especially during inflammation, remains incompletely understood. We performed flow cytometry, bulk and single-cell RNA-sequencing to profile ileal lamina propria and intraepithelial CD4 T cells (CD4CD8αα, regulatory T cells (Tregs), CD69 - and CD69 high Trm T cells) in controls and Crohn's disease (CD) patients (paired non-inflamed and inflamed)...

SARS-CoV-2, the virus responsible for COVID-19, has caused havoc around the world. While several COVID-19 vaccines and drugs have been authorised for use, these antiviral drugs remain beyond the reach of most low- and middle-income countries. Rapid viral evolution is reducing the efficacy of vaccines and monoclonal antibodies and contributing to deaths of some fully vaccinated persons. Others with normal immunity may have chosen not be vaccinated and remain at risk if they contract the infection. Vaccines may not protect some immunodeficient patients from SARS-CoV-2, who are also at increased risk of chronic COVID-19 infection, a dangerous stalemate between the virus and a suboptimal immune response...

C1 inhibitor (C1Inh) is a serine protease inhibitor involved in the kallikrein-kinin system, the complement system, the coagulation system and the fibrinolytic system. In addition to the plasma leakage observed in hereditary angioedema (HAE), C1Inh deficiency may also affect these systems, which are important for thrombosis and inflammation. The aim of this study was to investigate the thromboinflammatory load in C1Inh deficiency. We measured 27 cytokines including interleukins, chemokines, interferons, growth factors and regulators using multiplex technology...