Scandinavian Journal of Immunology最新文献

Food allergy may develop after both oral and skin exposure to food allergens. Identifying immunological features associated with the sensitisation route is important for understanding the extent to which patients are sensitised through the oral or skin route and may be required to improve food allergy immunotherapy. Thus, the present study aimed at comparing the immunological features of peanut sensitisation induced through the oral and skin route in Brown Norway (BN) rat models. Sensitisation to peanut protein extract (PPE) was induced via oral or skin administration in BN rats. Allergy development was analysed by ELISA for PPE- and major allergen-specific IgE levels and by ear swelling responses to native and denatured PPE. Intestinal and skin tissues were analysed by flow cytometry for immune cell compositions and by TaqMan PCR for the expression of cytokines. Oral and skin sensitisation showed distinct patterns of specific IgE against the major peanut allergens. Conformational IgE epitopes dominated both routes of sensitisation. Skin sensitisation was associated with the activation of T cells and the expansion of antigen presenting cells in both the intestine and skin, whereas oral sensitisation showed a limited effect on immune cell composition and activation. Oral and skin sensitisation were associated with different intestinal cytokine expression profiles. Oral and skin sensitisation drive different responses to the major peanut allergens and promote different immunological responses in the intestine.

The New Zealand (NZ) Common Variable Immunodeficiency Disorders (CVID) study (NZCS) is a long-term prospective cohort study, which seeks to better understand the proximal causes and sequelae of CVID. Patients were accepted to the NZCS if they had a diagnosis of CVID. After informed consent, clinical and demographic data were obtained by an interviewer-assisted questionnaire. Computerised case notes and laboratory results, linked to each patient's National Health Index (NHI) number, were also reviewed. In the current analysis, ethnic-specific data was obtained on the prevalence of CVID and its sequelae in NZ. One hundred and eight patients with a diagnosis of CVID were enrolled in the NZCS, comprising approximately 70% of patients known to have CVID in NZ. There was a much greater prevalence of bronchiectasis in Māori (79%) compared to Caucasian CVID patients (38%). Māori patients with CVID develop symptoms at a younger age and have an increased number of severe infections prior to diagnosis. Māori CVID patients with bronchiectasis had a higher prevalence of complete IgA deficiency compared to Caucasian CVID patients with bronchiectasis. In contrast to Caucasian patients with CVID, autoimmune and inflammatory sequelae were much less common in Māori. This study also demonstrated worsening diagnostic delays in patients with CVID in NZ. The Indigenous Māori of Aotearoa have a much more aggresssive early-onset, infection-only CVID variant compared to Caucasian New Zealanders.

X-linked agammaglobulinemia (XLA) is caused by Bruton tyrosine kinase gene mutations, leading to B-cell deficiency. This study aimed to investigate myeloid-derived suppressor cells (MDSCs) frequency, lymphocyte apoptosis and clinical significance in patients with XLA. The study comprised 46 paediatric (mean age: 9.9 ± 4.8 years) and 21 adult patients (24.6 ± 5.9 years). Total MDSCs (HLA-DR^-CD33⁺CD11b⁺) were subdivided into CD15⁺ polymorphonuclear (PMN-MDSCs) and CD14⁺ monocytic (M-MDSCs) and analysed by flow cytometry. The paediatric XLA patients had increased M-MDSCs and early apoptotic lymphocyte frequency compared to healthy subjects. The mean diagnostic delay was positively correlated with early apoptotic CD3⁺ and CD4⁺ T-cells. Seventeen patients (14 adults and 3 children) had bronchiectasis. PMN-MDSCs were higher in adult patients than in paediatric patients. Increased PMN-MDSCs in adults with XLA suggest the presence of chronic inflammation in patients with bronchiectasis. The study findings broaden understanding of XLA's complex immunopathology and highlight the need for more comprehensive immune monitoring of these patients beyond antibody production.

Cluster of differentiation 36 (CD36) is a multifunctional membrane protein receptor widely expressed on the surface of various immune and nonimmune cells in the body, and it belongs to the class B scavenger receptor family (SR-B2). The extracellular domain of CD36 can recognise and bind to various ligands, mediating a range of biological functions and participating in various physiological and pathological processes, including immune responses, lipid metabolism, cancer and inflammation. This review summarises the gene and protein structure of CD36 and its ligand-mediated biological functions. It further elucidates the role of CD36 in regulating immune responses, various metabolic processes and mechanisms, as well as the involved signalling pathways, providing a theoretical foundation for related biological research.

Psoriasis is an autoimmune disease of the skin with keratinocyte hyperproliferation and increased skin homing of immune cells. LL-37 is an antimicrobial peptide present at a high level in psoriasis patients. It is thought to participate in the induction of psoriasis and is a potential autoantigen. This study explores the chemokine receptor expression of T cells in psoriasis patients in the context of LL-37 bioavailability in the skin. Thus, chemokines secreted by peripheral blood mononuclear cells (PBMCs), cultured in a psoriasis-mimicking Th1 or Th17 microenvironment, are evaluated in association with LL-37 secretion. The results show that the chemokine receptors CXCR3, CCR4 and CCR6 were expressed at different levels by T cells depending on their expression of the skin-homing and retention markers cutaneous lymphocyte antigen (CLA) and CD103, respectively. A higher proportion of T cells from psoriasis patients expressed CCR6 compared to those from healthy controls, whereas a lower proportion of psoriatic T cells expressed CXCR3^hi. PBMCs stimulated in Th1 and Th17 mimicking microenvironments altered their secretion of many immune biomarkers, further modulated by the addition of LL-37. Principal component analysis revealed that the secretion of chemokines from PBMCs after Th1 stimulation clustered away from the secretion of chemokines after Th17 stimulation. Stimulation of CXCR3^hi expressing CD4⁺ T cells revealed less secretory potential than their CXCR3^neg expressing CD4⁺ T cells. In summary, LL-37 demonstrated remarkable abilities in modulating the secretion of immune biomarkers by PBMCs, which may cause a change in the microenvironment in the skin in psoriasis.

The metabolic programme of T cells is pivotal in determining their differentiation, development and immune function. T cells undergo distinct metabolic reprogramming at various stages. Effector T cells primarily utilise glycolysis to generate energy quickly, whereas memory T cells depend on fatty acid oxidation (FAO) to sustain long-term survival and enable rapid reactivation. This metabolic differentiation is regulated through metabolic reprogramming by adjusting nutrient utilisation to meet specific demands. Ketone bodies, FAO-derived metabolites, interact with glucose and amino acid metabolism to influence the function and differentiation of T cells and other immune cell subsets. The body's metabolic equilibrium is significantly influenced by dietary patterns. A medically designed dietary intervention that elevates ketone body levels can reshape T-cell metabolism, influencing their differentiation, development and immune functions. This metabolic modulation suggests a potential interplay between nutritional strategies and T-cell immunotherapy applications, especially in the context of tumour immunology. This review explores ketone body metabolism and its impact on T-cell function, offering insights into the clinical use of diet-induced ketosis for T-cell immunotherapy. It also emphasises the potential of metabolic reprogramming to boost T cell performance and improve the efficacy of immunotherapy.

Natural Killer T-like cells are T lymphocytes characterised by the expression of CD56 accompanied by perforin and granzyme B production, typical of cytotoxic cells and the innate immunity compartment. Imbalance in their distribution could occur in pathological conditions, including solid or haematological cancers, autoimmune disorders and metabolic diseases; therefore we aimed to define age-matched reference values of the NKT-like population. NKT-like cell count and their expression of CD4 and CD8 surface antigens were evaluated in 2208 subjects by flow cytometry, with a lyse-no-wash protocol in a CE-IVD workup. Outpatients without alteration of any laboratory test and adult healthy volunteers were used to determine NKT-like age-matched reference values; a total of 490 subjects divided into six age ranges were finally enrolled. We defined reference values for NKT-like cells in adult and in 5 age-matched paediatric control groups. NKT-like cell number increases with age both in percentage and absolute count. While NKT-like/CD8+ cells increased with age, NKT-like/CD4+ cells showed an opposite trend. Similarly, double-positive cells (NKT-like/CD4+ CD8+) gradually decreased with age, while double-negative cells (NKT-like/CD4-CD8-) increased up to 16 years and then decreased in adults. Ultimately, we evaluate adult and paediatric patients with NKT-like cell count outside normal ranges derived here to highlight the principal associated conditions that may be involved. Our paper is a first step toward the definition of robust reference values for NKT-like cell subpopulations under the CE-IVD conditions. Providing NKT-like cell number and frequency in the diagnostic report appears helpful to better delineate the immune profile of patients.

The rapid rollout of mRNA-based COVID-19 vaccines, including Pfizer-BioNTech's BNT162b2 and Moderna's mRNA-1273, has been instrumental in curbing the pandemic, demonstrating high efficacy and safety in the general population. However, concerns regarding neurological adverse effects, particularly in individuals with epilepsy (PWE), warrant scrutiny. Clinical data from case reports, multicenter studies, and meta-analyses (encompassing over 3000 PWE) indicate that most tolerate vaccination well, with seizure worsening in approximately 5% of cases, often transient and lower than post-COVID-19 infection rates. Rare severe events, such as status epilepticus, highlight vulnerabilities, though background seizure incidence remains comparable or lower than natural rates. This review examines potential neuroimmune mechanisms linking mRNA vaccination to seizure exacerbation, emphasising immune activation, neuroinflammation, and epileptogenesis. mRNA vaccines utilise lipid nanoparticles (LNPs) to deliver spike protein-encoding mRNA, eliciting robust immune responses. Potential triggers for seizures include cytokine storms (e.g., IL-1β, TNF-α, IL-6), blood-brain barrier (BBB) disruption, molecular mimicry with neuronal antigens, and autoantibody production, which may heighten neuronal hyperexcitability in susceptible individuals. Neurological side effects, including Bell's palsy, transverse myelitis, and herpes zoster reactivation, are more prevalent in mRNA platforms, potentially tied to LNP-induced inflammation or cross-reactive immunity. While evidence supports vaccination benefits outweighing risks for PWE, gaps persist in understanding individual predispositions. Future research should prioritise longitudinal studies, EEG monitoring, and AI-driven approaches for personalised risk assessment, mRNA optimisation, and pharmacovigilance. Integrating multi-omics and computational modelling could enhance vaccine safety, ensuring equitable protection for vulnerable populations.

Immunology progresses not merely by accumulating data but by evolving the conceptual lenses through which those data are interpreted; yet for six decades the self-non-self/infectious-non-self (SNS/INS) paradigm-casting allogeneity as activating signal and 'self' as intrinsically tolerogenic-has dominated research design, peer review and curriculum. This, in turn, systematically amplifies concordant findings while attenuating evidence for tissue integrity, metabolic, symbiotic and network-centric cues. This conceptual monoculture appears as a hidden dogma that impedes breakthroughs in our understanding of the immune system and the development of curative therapies. By institutionalising theoretical immunology as a formal discipline and treating models as explicit, testable tools rather than hidden assumptions, immunologists can sharpen hypothesis generation and achieve a better understanding of existing data. This essay provides an overview of empirically grounded theoretical models to counter monoculture, clarify how frames shape interpretation, and expand the field's conceptual toolkit.