Immunology: White blood cells show their stripes

August 28, 2013, Agency for Science, Technology and Research (A*STAR), Singapore
Immunology: White blood cells show their stripes
Discovery of the CD11b+ subset (green) of murine dendritic cells and its direct human counterpart (not shown) could lead to improved therapeutics. Credit: A*STAR Singapore Immunology Network

For the human immune system to work effectively, the body must be able to distinguish invading pathogens, such as fungi and bacteria, from its own healthy tissue. A group of white blood cells known as dendritic cells (DCs) has a critical role in this task: DCs recognize pathogens then activate and regulate the immune system accordingly. Immunologists therefore believe that DCs could be harnessed for new therapies against fungal and bacterial infections, as well as autoimmune diseases such as multiple sclerosis.

Florent Ginhoux and co-workers at the A*STAR Singapore Immunology Network, together with researchers in the UK, United States and Japan, have identified a subset of DCs that exists in mouse and human mucosal tissues. The murine subset is called CD11b+ and the human equivalent is called CD1c+. The existence of similar in the two species will assist in translating the results of murine experiments to human biology and also further the development of clinical therapies.

Contamination by other cell types in previous studies limited the true understanding of the function of CD11b+ cells, Ginhoux notes. "In this study, we found new markers to specifically identify CD11b+ DCs."

Parts of the body that are exposed to the external environment, such as the lungs and gut, contain DCs (see image). They act as messengers, presenting fragments of pathogens to other called CD4 T- that trigger appropriate immune responses. One particular T-helper, Th17, in concert with DCs, specializes in activating the protective response to fungal or bacterial infections.

"We found that CD11b+ DCs secrete a specific cytokine protein named interleukin-23 (IL-23). This protein induces and governs Th17 cells that secrete a second cytokine—IL-17—a very potent against fungi in the lungs of mice as well as of humans," explains Ginhoux.

During infections that fight and clear pathogens, IL-17 can be very powerful. If cytokine IL-23 secretion is unregulated, however, it induces exacerbated Th17 responses because of an excess of IL-17 release. This regulation failure has been linked to the development of psoriasis, Crohn's disease and multiple sclerosis. Controlling the activity of DCs that regulate IL-23 and subsequent Th17 cell responses could therefore prove useful therapeutically.

"There are two major applications for this research," says Ginhoux. Firstly, a vaccine strategy targeting CD11b+ DCs to trigger a potent IL-17-dependent immune response could prevent fungal and bacterial infections. Secondly, selectively inhibiting CD11b+ DCs may lead to better control of IL-17-dependent autoinflammatory disorders.

Explore further: Discovery of a new class of white blood cells uncovers target for better vaccine design

More information: Schlitzer, A., McGovern, N., Teo, P., Zelante, T., Atarashi, K. et al. IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses, Immunity 38, 970–983 (2013). www.cell.com/immunity/abstract … 1074-7613(13)00205-7

Related Stories

Discovery of a new class of white blood cells uncovers target for better vaccine design

July 17, 2013
(Medical Xpress)—Scientists at A*STAR's Singapore Immunology Network (SIgN) have discovered a new class of white blood cells in human lung and gut tissues that play a critical role as the first line of defence against harmful ...

Recently uncovered human counterparts to a subset of mouse immune cells may enable better vaccination strategies

October 24, 2012
Mice have made an immeasurable contribution to medicine and our overall understanding of human disease. This animal model is not without its limitations, however, and scientists are continually learning about important ways ...

Scientists discover dendritic cells key to activating human immune responses

July 16, 2012
Scientists at A*STAR’s Singapore Immunology Network (SIgN), in collaboration with Newcastle University, UK, the Singapore Institute of Clinical Sciences and clinicians from multiple hospitals in Singapore, have identified ...

Jump-starting cheaper cancer vaccines

September 26, 2012
Dendritic cells (DCs)—workhorses of the immune system—derived from human embryonic stem cells (hESCs) may provide an economical way of generating off-the-shelf therapeutic vaccines against cancers, according to research ...

Langerhans cells migrate to their final destination in multiple waves at different stages of embryonic development

August 29, 2012
As our primary interface with the outside world, the skin needs to be able to protect itself against infectious threats. Specialized cells known as Langerhans cells (LCs) (see image) are an essential component of this defense, ...

A novel mechanism that regulates pro-inflammatory cells identified

August 10, 2011
New research led by Derya Unutmaz, MD associate professor, the Departments of Pathology, Medicine, and Microbiology at NYU School of Medicine and Mark Sundrud, PhD, of Tempero Pharmaceuticals, Inc., has identified a novel ...

Recommended for you

Paracetamol use in infancy is linked to increased risk of asthma in some teenagers

September 17, 2018
Children who take paracetamol during their first two years of life may be at a higher risk of developing asthma by the age of 18, especially if they have a particular genetic makeup, according to new research presented at ...

Cord blood clue to respiratory diseases

September 15, 2018
New research has found children born in the last three months of the year in Melbourne may have a greater risk of developing respiratory diseases such as asthma.

FRESH program combines basic science with social benefits for women at risk of HIV

September 14, 2018
A program established by investigators from the Ragon Institute of Massachusetts General Hospital (MGH), MIT and Harvard is addressing the persistently elevated risk of HIV infection among young women in South Africa from ...

Dietary fiber reduces brain inflammation during aging

September 14, 2018
As mammals age, immune cells in the brain known as microglia become chronically inflamed. In this state, they produce chemicals known to impair cognitive and motor function. That's one explanation for why memory fades and ...

Research reveals link between immunity, diabetes

September 14, 2018
When it comes to diet-induced obesity, your immune system is not always your friend.

Immune response mechanism described for fate determination of T cells

September 13, 2018
After a pathogen infects the body, the immune system responds with a remarkable—and remarkably complicated—cascade of events.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.