Immunoglobulin E: not just a bystander in lupus?

IgE antibodies are mostly known for their pathophysiological role in allergic reactions and in certain immune deficiencies referred to as hyper-IgE syndromes. In a study published in The Journal of Experimental Medicine in September, Dema et al. find that IgE deficiency ameliorates the signs of autoimmune inflammation and organ damage in a mouse model of systemic lupus erythematosus.

STING-associated autoinflammatory disease

A study published in the New England Journal of Medicine describes an autoinflammatory syndrome associated with mutations in the gene encoding STING. Dubbed SAVI, for STING-associated vasculopathy with onset in infancy, the disease is characterized by systemic inflammation, severe cutaneous vasculopathy, interstitial lung disease, and a type 1 interferon signature.

Vitamin A and the immune system

Vitamin A is known to play an important role in embryonic and early childhood development. Childhood blindness is perhaps the most widely known example of the deleterious effects of vitamin A deficiency in children.

It has been known for a while that vitamin A and its metabolite, retinoic acid, can influence immunity. In the past decade, many studies have highlighted the role of retinoic acid in regulating migration and differentiation of immune cell subsets in the gastrointestinal tract.

Two papers published this year in Science and Nature have now looked at the effect of vitamin A deficiency on subsets of immune cells called innate lymphoid cells and lymphoid tissue inducer cells, and at how vitamin A deficiency and impaired retinoic acid signaling affects immune responses and immune system development.

A new Treg subset on the block, and a clue to understand IFNβ efficacy in the treatment of multiple sclerosis

IFNβ has been used in the treatment of multiple sclerosis (MS) for about two decades, however the molecular mechanisms underlying its efficacy in preventing and/or limiting relapses or disease progression are poorly understood. Perhaps even more importantly, it also remains unknown why a subset of patients with MS does not respond to IFNβ therapy.

In a study recently published in Nature Medicine, researchers from the University of Copenhagen offer a new clue to understand how IFNβ exerts its therapeutic effect in MS by describing a new type of regulatory T  (Treg) cells.

Called FoxA1⁺ Treg cells,

Human Th9 cells – Who, what and where

Th9 cells, a subset of T helper cells producing the cytokine IL-9, were first characterized in mice five years ago. In a study recently published in Science Translational Medicine, Schlapbach et al. investigate the relevance of Th9 cells in humans and their potential contribution to immune responses in the skin.

Helper T cells (CD4+ T cells) play an important role in the orchestration of adaptive immune responses by secreting lineage-specific cytokines and steering the immune response to best address the threat at hand. Several helper T cell (Th) subsets have been described,

Cancer immunosurveillance gone awry?

The potential relationship between cancer and autoimmunity is intriguing. Patients with certain autoimmune rheumatic diseases are known to have an increased risk of developing certain malignancies. For example, patients with systemic lupus erythematosus have a 4-5 fold increased risk of developing lymphoma compared with the general population, and the risk is even greater for patients with primary Sjögren’s syndrome. Conversely, treatment of cancer with IFNα chemotherapy is known to induce a lupus-like syndrome in 5-20% of patients. Some rheumatic diseases have also been observed to occur coincidentally with cancer.

In a paper published this week in Science, Joseph et al. raise the intriguing possibility that neoantigens created by somatic mutations occurring in tumors may generate an autoreactive immune response, laying the foundation for potential autoimmune disease development.

How Academia Resembles a Drug Gang

Alexandre Afonso

In 2000, economist Steven Levitt and sociologist Sudhir Venkatesh published an article in the Quarterly Journal of Economics about the internal wage structure of a Chicago drug gang. This piece would later serve as a basis for a chapter in Levitt’s (and Dubner’s) best seller Freakonomics: A Rogue Economist Explores the Hidden Side of Everything (P.S.) The title of the chapter, “Why drug dealers still live with their moms”, was based on the finding that the income distribution within gangs was extremely skewed in favor  of those at the top, while the rank-and-file street sellers earned even less than employees in legitimate low-skilled activities, let’s say at McDonald’s. They calculated 3.30 dollars as the hourly rate, that is, well below a living wage (that’s why they still live with their moms). [2]

If you take into account the risk of being shot by rival gangs, ending up in jail or…

View original post 2,048 more words

Regulatory T cell stability and ubiquitin-mediated FOPX3 degradation

Two studies published in Immunity in August identify Stub1 and USP7 as two components of the ubiquitin-proteasome system that modulate FOXP3 protein turnover. The findings point to new mechanisms by which inflammatory stimuli may affect regulatory T cell stability and suppressive capacities.

A fundamental aspect of the immune system is the maintenance of self-tolerance. Self-reactive immune responses must be held in check to avoid damage to host tissues and establishment of autoimmune diseases. Several mechanisms and components contribute to the maintenance of tolerance, amongst which regulatory T (Treg) cells.

About a decade ago, the transcription factor FOXP3 was found to be critical for the development of Treg cells and the maintenance of their suppressive properties.

Giant viruses

Following their discovery in the late 19^th century, viruses were quickly put aside as simple particles, mere small packages of genetic material unable to replicate by themselves and therefore not belonging to the living world. Ten years ago, a French research team discovered a giant Amoeba-infecting virus that contained a DNA genome larger in size and gene content than those of some bacteria. They called it Mimivirus (for microbe mimicking virus) and over the following years identified other giant Mimivirus-like viruses. The members of this new family, termed Megaviridae, appeared to harbor enzymes usually considered hallmarks of cellular organisms, such as amino acid transfer RNA ligases. Together with their large genome, these unusual features of Mimiviruses challenged the way people used to think of viruses, especially when compared to cellular organisms.

In an article published in Science on July 19, 2013, the same research team now describes two new giant viruses, one of them harboring the largest genome ever seen in a virus (and even bigger than those of some parasitic eukaryotes and bacteria).

A new player in the IL-17 game

In a study published in May in Nature Immunology, a team of Argentinian and American scientists shows that B cells are capable of producing IL-17 in response to infection by the parasite Trypanosoma cruzi.

The current textbook knowledge tells us that the main role of B cells in response to an infection is to produce antibodies to neutralize and help get rid of the pathogen. In parallel, it also tells us that production of the IL-17 cytokine by the Th17 subset of helper T cells and innate lymphoid cells is essential to the control of infections by extracellular pathogens,