Lipids produced within the thymus give immune cells the initial boost they need to fight off infection

Immunology: The kick-starters of immune cells
The thymus is a central component of the immune system, and is the site where selected iNKT cells undergo initial activation before migrating to other sites in the body. Credit: iStockphoto.com/janulla

Semi-invariant natural killer T (iNKT) cells wage war against infectious threats, attacking microbial cells and generating signals that enable other immune cells also to respond aggressively. iNKT cells initially undergo activation in the thymus; after being 'switched on' via interaction with certain antigens, they undergo an initial population expansion and then migrate to peripheral immune sites where they proliferate further so they can mount an effective defense.

Some of these activating triggers are foreign in origin, such as bacterial membrane components. However, iNKT cells can also be activated by lipids produced within the thymus itself, as demonstrated in new research from a team led by Gennaro De Libero of the A*STAR Singapore Immunology Network. Previous research had indicated that such 'self' lipids might be an important stimulus. De Libero's team therefore began by treating cultured mouse iNKT cells with lipids isolated from thymic cells and looking for biological signatures of activation. "We found that unusual lipids are important for thymic selection, and that these lipids are produced within unique called peroxisomes," he says.

A peroxisomal enzyme called glyceronephosphate O-acyltransferase (GNPAT) plays a central role in producing these particular lipids. Accordingly, the researchers observed that iNKT cell maturation tended to stall in mice lacking GNPAT, and these animals had considerably fewer functional iNKT cells than normal mice. Subsequent transplantation experiments demonstrated that immature iNKT cells from wild-type mice are less likely to reach full maturity when grafted into thymuses of GNPAT-deficient mice. Collectively, these experiments demonstrate that a substantial subset of developing iNKT cells is dependent on interactions with peroxisomally produced lipids in the thymus in order to undergo full activation.

Despite the team's revelation of  insightful details about the development of these important , a number of mysteries remain—for example, how mature iNKTs learn to stop targeting the that switched them on in the first place. "Now that we know the stimulatory self lipids, we can address the mechanisms which reduce iNKT reactivity against them in the periphery," explains De Libero. This would provide a means to avoid autoimmune attacks.

In parallel, he and his colleagues intend to determine whether foreign lipids also trigger immune cell maturation via a similar mechanism. "For example, T cells that recognize mycobacterial lipids are important in protecting people from tuberculosis," he says, "and it will be important to study how these cells are selected and mature within the thymus."

More information: Facciotti, F., Ramanjaneyulu, G. S., Lepore, M., Sansano, S., Cavallari, M., et al. Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus. Nature Immunology 13, 474–480 (2012). www.nature.com/ni/journal/v13/n5/abs/ni.2245.html

add to favorites email to friend print save as pdf

Related Stories

Research describes advantages of new vaccine adjuvant

Dec 12, 2011

New research from the laboratory of Dr. Elizabeth Leadbetter at the Trudeau Institute may lead to a whole new class of vaccines. Dr. Leadbetter's lab has discovered new properties of a potential vaccine adjuvant that suggest ...

Cigarette smoke impairs ability to fight disease

Mar 04, 2011

University College Dublin researchers in the obesity immunology research group in the Education Research Centre, St Vincent's University Hospital led by Professor Donal O’Shea have demonstrated for the first time that ...

Improving psoriasis with GLP-1 analogue therapy

Dec 13, 2011

(Medical Xpress) -- UCD clinician scientists and researchers from NUI Maynooth and Trinity College led by Conway Fellow, Professor Donal O’Shea have reported an improvement in the severity of psoriasis in patients following ...

Using cancer's weapons against it

Oct 08, 2010

(PhysOrg.com) -- Tumours seem to pacify our immune system by tapping into our bodies’ codes, but we may be able to use this trick against them in our bid to hunt them down.

Recommended for you

Invading worms cause the body to shut down defenses

Oct 20, 2014

When parasitic worms invade muscle tissue, white blood cells called eosinophils rush to the scene. A study published in the Journal of Immunology this month reveals that these cells actually start a chai ...

User comments