Small RNA molecules identify T-helper cells and point to a new allergy treatment

I haven’t written a post in a long, long while. Wired feelings being back at the keyboard. As most of you know I have been recently experienced a number of changes, including moving into a new country and starting a new line of research for my first postdoc in London.

I thought there was no better way to re-boost my pop-science writing then illustrate to you the latest paper from my new lab, lead by Mark Wilson, at the National Institute for Medical Research (NIMR) – just published in PNAS.

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T-helper cells coordinates the immune response talking to other immune cells.

Mark’s lab works on the type of immunity that defends you against big, nasty worms (like helminths) and, at the same time, it is responsible for one of the most common chronic condition in the world: allergies. This immunity (named Type II) is controlled by the “T-helper“, a group of cells that can be compared to strict “generals” that shout commands to other cells of the immune system to tell them what to do. T-helper are plastic cells, that change their instructions in accordance to the challenge your body is facing. Type II T-helper cells (or Th2 cells) are T-helper that shout the specific string of commands necessary to attack certain infections, including worms, but uncontrolled Th2 cells are also responsible for allergic reaction.

It is of great interest understanding the type II immunity, particularly what makes Th2 what they are, in the attempt to block this process for therapeutic purposes.

Mark’s lab is interested in micro-RNA (miRNA), a group of small molecules that function as “messenger-RNA sponges”, and prevent the translation of mRNA into proteins. Due to their characteristic, miRNA are considered epi-regulator of cells, and one single miRNA can control numerous functions at once.

A human worm helminths – credits: BPhealthcare

To look at the types of miRNA present in T-helper cells, particularly in Th2, Mark’s lab used an array of genetic tools to isolate all the different subset of T-helpers known: Th1, Th2, Th9, Th17 and Treg. Scientists can generate Th2 cells in vitro, in animal models of helminth infection or following allergen exposure. Interestingly, the paper reports that different methods make Th2 cells with different miRNA profile, uncovering a new layer of control for these cells. Of the numerous new miRNA identified, the miR-155 was found to be important for the Th2-mediated immunity, and inhibition of this miRNA ameliorates allergy in an animal model.

The strength of the paper is to combine a large set of very different models to accurately isolate distinct T-helper subtypes, and to perform a miRNA and mRNA analysis of all these cells in parallel. Though many miRNA were experimentally validated in the study, many other remains to be characterize in the contest of type II immunity, and to further explore their therapeutic potential.

I look forward to continue this line of research, together with my new colleagues. Excited by the challenge!

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