Jonatan Leffler

Mechanisms of Acute Viral Respiratory Illness in Children (MAVRIC)

Impaired interferon response in plasmacytoid dendritic cells from children with persistent wheeze

Impaired interferon response and allergic sensitization may contribute to virus-induced wheeze and asthma development in young children. Plasmacytoid dendritic cells play a key role in antiviral immunity as critical producers of type I interferons. 

Egg-sensitised infants have elevated CD4+ effector memory T regulatory cells from birth

IgE-mediated sensitisation to egg is common in infants. In some cases, the processes leading to egg sensitisation are established in early life, even before introduction to solid foods. The underlying mechanisms remain poorly understood. 

Editorial: The relationship between puberty and immune-driven disease

The way the immune system operates differs between males and females. This is due to both differential expression of immune-related genes from the sex chromosomes as well as the immune modulatory properties of sex hormones. Together, these effects contribute to a skewed prevalence of disease and disease course between males and females, including allergic-, infectious-, autoimmune-, and cancerous disease.

Assessing neutrophil subsets in autoimmune disease: Moving away from relying on density?

Neutrophils are the most abundant immune cell in circulation. However, due to a number of technical challenges for researchers, including the neutrophil's short lifespan and difficulties with preservation, they are often discarded during blood processing and thus ignored in cohort studies. As such, the contribution of neutrophils to disease and their involvement in disease mechanisms is less explored compared with other immune cell types.

LPS binding protein and activation signatures are upregulated during asthma exacerbations in children

Asthma exacerbations in children are associated with respiratory viral infection and atopy, resulting in systemic immune activation and infiltration of immune cells into the airways. The gene networks driving the immune activation and subsequent migration of immune cells into the airways remains incompletely understood. Cellular and molecular profiling of PBMC was employed on paired samples obtained from atopic asthmatic children during acute virus-associated exacerbations and later during convalescence.

Potential immunological effects of gender-affirming hormone therapy in transgender people – an unexplored area of research

There are well-described sex-based differences in how the immune system operates. In particular, cisgender (cis) females have a more easily activated immune system; associated with an increased prevalence of autoimmune diseases and adverse events following vaccinations. Conversely, cis males have a higher threshold for immune activation, and are more prone to certain infectious diseases, such as coronavirus disease (COVID-19).

Tissue-resident memory T cells in the era of (Neo) adjuvant melanoma management

Tissue-resident memory T (TRM) cells have emerged as key players in the immune control of melanoma. These specialized cells are identified by expression of tissue retention markers such as CD69, CD103 and CD49a with downregulation of egress molecules such as Sphingosine-1-Phosphate Receptor-1 (S1PR1) and the lymphoid homing receptor, CD62L.

Epstein–Barr virus infection, B-cell dysfunction and other risk factors converge in gut-associated lymphoid tissue to drive the immunopathogenesis of multiple sclerosis: a hypothesis

Multiple sclerosis is associated with Epstein–Barr virus (EBV) infection, B-cell dysfunction, gut dysbiosis, and environmental and genetic risk factors, including female sex.

Circulating Memory B Cells in Early Multiple Sclerosis Exhibit Increased IgA+ Cells, Globally Decreased BAFF-R Expression and an EBV-Related IgM+ Cell Signature

Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system that results in demyelination of axons, inefficient signal transmission and reduced muscular mobility. Recent findings suggest that B cells play a significant role in disease development and pathology. To further explore this, B cell profiles in peripheral blood from 28 treatment-naive patients with early MS were assessed using flow cytometry and compared to 17 healthy controls.

Sex-Specific Environmental Impacts on Initiation and Progression of Multiple Sclerosis

The immunological mechanisms that contribute to multiple sclerosis (MS) differ between males and females. Females are 2-3 times more likely to develop MS compared to males, however the reason for this discrepancy is unknown. Once MS is established, there is a more inflammatory yet milder form of disease in females whereas males generally suffer from more severe disease and faster progression, neural degradation, and disability.

IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming

High risk for virus-induced asthma exacerbations in children is associated with an IRF7lo immunophenotype, but the underlying mechanisms are unclear. Here, we applied a Systems Biology approach to an animal model comprising rat strains manifesting high versus low susceptibility to experimental asthma, induced by virus/allergen coexposure, to elucidate the mechanism(s)-of-action of the high-risk asthma immunophenotype.

FcgammaRIIb Expression Is Decreased on Naive and Marginal Zone-Like B Cells From Females With Multiple Sclerosis

B cells are critical to the development of multiple sclerosis (MS), but the mechanisms by which they contribute to the disease are poorly defined. We hypothesised that the expression of CD32b (FcγRIIb), a receptor for the Fc region of IgG with inhibitory activities in B cells, is lower on B cell subsets from people with clinically isolated syndrome (CIS) or MS. CD32b expression was highest on post-naive IgM+ B cell subsets in healthy controls. For females with MS or CIS, significantly lower CD32b expression was identified on IgM+ B cell subsets, including naive and IgMhi MZ-like B cells, when compared with control females. Lower CD32b expression on these B cell subsets was associated with detectable anti-Epstein Barr Virus viral capsid antigen IgM antibodies, and higher serum levels of B cell activating factor. To investigate the effects of lower CD32b expression, B cells were polyclonally activated in the presence of IgG immune complexes, with or without a CD32b blocking antibody, and the expression of TNF and IL-10 in B cell subsets was assessed.

Narrowband UVB phototherapy reduces TNF production by B-cell subsets stimulated via TLR7 from individuals with early multiple sclerosis

At the end of a 60-day course of narrowband UVB phototherapy, administered to individuals with early multiple sclerosis, there were changes in the relative proportions of circulating B-cell subsets. This study investigated phototherapy-associated changes to cytokine responses of B cells when exposed to a TLR7 ligand.

Oestrogen amplifies pre-existing atopy-associated Th2 bias in an experimental asthma model

The role of oestrogen in experimental atopic asthma, and guide future research on sex-related variations in atopic asthma susceptibility/intensity

Progressive increase of FcεRI expression across several PBMC subsets is associated with atopy and atopic asthma within school-aged children

The expression pattern of FcεRI on DC and basophils differentiates asthmatic from non-asthmatic atopic children

Quantification of Serum Ovalbumin-specific Immunoglobulin E Titre via in vivo Passive Cutaneous Anaphylaxis Assay

We describe herein a highly reproducible in vivo passive cutaneous anaphylaxis assay using Sprague Dawley rats for the quantification of ovalbumin-specific IgE

Early Life Ovalbumin Sensitization and Aerosol Challenge for the Induction of Allergic Airway Inflammation in a BALB/c Murine Model

This protocol adapted an experimental animal model of disease for sensitization to ovalbumin during the immediate post-weaning period beginning at 21 days of age

Transplacental immune modulation with a bacterial-derived agent protects against allergic airway inflammation

These data provide proof of concept supporting the rationale for developing transplacental immune reprogramming approaches for primary disease prevention

Basophil counts in PBMC populations during childhood acute wheeze/asthma are associated with future exacerbations

Our findings suggest that the proportion of degranulated basophils can also be associated with recurrent exacerbations

Immunological processes driving IgE sensitisation and disease development in males and females

In this review, we discuss recent mechanistic studies casting further light on how the expression of sex hormones may influence the innate and adaptive immune system

Functional differences in airway dendritic cells determine susceptibility to IgE-sensitization

Respiratory IgE-sensitization to innocuous antigens increases the risk for developing diseases such as allergic asthma.

Plasma C4d as marker for lupus nephritis in systemic lupus erythematosus

In the present study, we sought to evaluate the complement activation product C4d as a marker for lupus nephritis in systemic lupus erythematosus (SLE).

Protection against maternal infection-associated fetal growth restriction: Proof-of-concept with a microbial-derived immunomodulator

This study suggests that broad-spectrum protection-of-pregnancy against infection-associated inflammatory stress represents an achievable therapeutic goal

The complement system in systemic lupus erythematosus: An update

The complement system plays a major role in the autoimmune disease, systemic lupus erythematosus (SLE). This review highlights the many roles of complement for

Factor H autoantibodies in patients with antiphospholipid syndrome and thrombosis

This study analyzed autoantibodies to complement factor H (FH) in 2 independent cohorts of patients with antiphospholipid syndrome.

A subset of patients with systemic lupus erythematosus fails to degrade DNA from multiple clinically relevant sources.

Patients with systemic lupus erythematosus (SLE) have a decreased ability to clear cell remnants and multiple deficiencies in the ability to degrade cellular...