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.

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,

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.

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,

Helios and negative selection of CD4+ cells in the thymus

Helios is a transcription factor belonging to the Ikaros family and is expressed in most Foxp3⁺ regulatory T cells in the thymus. In a study published in The Journal of Experimental Medicine, Daley et al. show that Helios can also be used to differentiate between positive and negative selection of CD4⁺ thymocytes. Helios is induced in strongly self-reactive thymocytes, along with the pro-apoptoic protein Bim, during negative selection. Conversely, its expression decreases during positive selection. The authors also describe two distinct waves of clonal deletion in which Helios and Bim are co-induced: one happening in CCR7^– thymocytes and featuring the expression of the inhibitory receptor PD-1 ; the other happening at a subsequent developmental stage in CCR7⁺ thymocytes and characterized by the Card11-mediated expression of several NF-kB-dependent T cell survival and growth genes. In the latter, key mediators such as IL-2 and Myc are however not induced and the thymocytes do not proliferate. The authors suggest that this represents a “hollow activation” that sets the stage for some of these cells to become Foxp3⁺ T regulatory cells.

Reference
Helios marks strongly autoreactive CD4⁺ T cells in two major waves of thymic deletion distinguished by induction of PD-1 or NF-κB. Daley SR, Hu DY, Goodnow CC. J Exp Med. 2013 Feb 11;210(2):269-85.
PMID: 23337809