Press releases
Please quote Nature Immunology as the source of these items.
The October 2007 issue of Nature Immunology is available online.
October 2007
Stop that itch!
Immune cells in the skin secrete a chemical that limits the inflammatory response to poison ivy and sunburn, according to a report online in this week's Nature Immunology.
Steve Galli and colleagues look at how the immune system responds to irritants such poison ivy and poison oak or to sunburn, all of which can lead to blistering of the skin. Their research identifies mast cells, a form of immune cell that resides in the skin, as the source of interleukin 10 (IL-10), a molecule known to suppress immune responses. Mice that lack mast cells or have mutant mast cells that are unable to make IL-10 develop larger skin lesions, which last much longer, than those of normal mice upon exposure to the irritant found in poisonous plants. The mutant mice also display higher numbers of T cells recruited to the affected skin lesions.
The work identifies a new role for mast cells, which have been previously associated with releasing mediators of allergic reactions. The authors utilize these findings to manipulate mast cell release of IL-10 in settings of skin inflammation and irritation to limit further damage. These findings might lead to new therapies for skin damage.
Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B
Michele A Grimbaldeston, Susumu Nakae, Janet Kalesnikoff, Mindy Tsai & Stephen J Galli
Published online: 02 September 2007 | doi 10.1038/ni1503
Restraining allergic responses
A cellular process crucial for preventing allergy is presented in a paper published online this week in Nature Immunology.
Certain varieties of immune cells release interleukin 4, a protein that, upon binding to its receptor, triggers signals that promote hallmark features of allergy. Yoshinori Fukui and colleagues show that interleukin 4 receptors expressed on the surface of immune cells called T cells are quickly internalized, directed along the complex network of protein 'fibres' that support T cell structure and shape, and ultimately routed into cellular compartments for degradation. This 'harness' on interleukin 4 expression is interrupted in T cells lacking Dock2, a protein responsible for regulating the 'trafficking' of internalized cargo. As a result Dock2-deficient T cells display excessive amounts of interleukin-4 receptors and Dock2-deficient mice suffer from spontaneous allergic inflammation. Whether Dock2 regulates the intracellular fate of other T cell surface proteins remains for future investigations.
T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-alpha subunit controlled by the Rac activator Dock2
Yoshihiko Tanaka, Shinjiro Hamano, Kazuhito Gotoh, Yuzo Murata, Yuya Kunisaki, Akihiko Nishikimi, Ryosuke Takii, Makiko Kawaguchi, Ayumi Inayoshi, Sadahiko Masuko, Kunisuke Himeno, Takehiko Sasazuki & Yoshinori Fukui
Published online: 02 September 2007 | doi 10.1038/ni1506
Dialling up damage responders
Certain cells of the immune system more readily tolerate damage to their genes than do other cells, up to a point. New research in Nature Immunology shows the protein BCL6, expressed in antibody-producing B cells, senses how much DNA damage is occurring inside these cells and activates repair pathways when damage becomes excessive.
BCL6 is a repressor that blocks expression of DNA repair enzymes in the presence of small amounts of damage. This suppression is beneficial to the B cells as these cells can 'fine-tune' their antibody responses by mutating the antibody genes or undergoing what is called 'class switch recombination', a genetic rearrangement that allows different types of antibodies to be produced.
Riccardo Dalla-Favera and colleagues show excessive DNA damage in these B cells can be recognized by BCL6. BCL6 acts as a 'damage-sensitive' resistor that, once tipped beyond a threshold amount of accumulated DNA breaks, initiates a pathway that leads to its own destruction and turns on repair enzymes. These findings further our understanding of BCL6, which is commonly found to be mutated in forms of B cell cancers, and may thereby be instructive in designing therapies to blunt BCL6 activity in these cancers.
Genotoxic stress regulates expression of the proto-oncogene Bcl6 in germinal center B cells
Ryan T Phan, Masumichi Saito, Yukiko Kitagawa, Anthony R Means & Riccardo Dalla-Favera
Published online: 09 September 2007 | doi 10.1038/ni1508
Stem cells have nervous impulses
Blood stem cells become activated in response to signals released by nerve cells according to research published online this week in Nature Immunology.
Tsvee Lapidot and colleagues report bone marrow stem cells express dopamine receptors. Release of neurotransmitters, as occurs during times of stress, triggers the blood cells to divide and migrate from their protected bone marrow environment. Treatment of mice with dopamine or other neurotransmitters led to increased numbers of these stem cells in bone marrow and in the blood circulation. Neurotransmitter stimulation of human bone marrow cells likewise increased their engraftment potential upon transplantation into 'humanized mouse' recipients, whose immune system is reconstituted by the human cells. Such findings might translate to increased efficiency of therapies that require bone marrow transplantation.
Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34+ cells through Wnt signaling
Asaf Spiegel, Shoham Shivtiel, Alexander Kalinkovich, Aya Ludin, Neta Netzer, Polina Goichberg, Yaara Azaria, Igor Resnick, Izhar Hardan, Herzel Ben-Hur, Arnon Nagler, Menachem Rubinstein & Tsvee Lapidot
Published online: 09 September 2007 | doi 10.1038/ni1509
Delicate and dynamic immunological equilibrium
Immune cells patrolling the microbe-rich intestine are able to 'tolerate' harmless, microorganisms while attacking and eliminating potentially dangerous pathogens. Work published online this week in Nature Immunology deepens our understanding of how this process occurs.
Previous work implicates immune cells called regulatory T cells in enforcing immunological tolerance to harmless or ‘commensal’ gut microbes. Bali Pulendran and colleagues pinpointed particular populations of gut ‘accessory’ cells called macrophages and dendritic cells which, although located adjacent to each other in the gut mucosa, exert opposite immune functions. Macrophages promote production of regulatory T cells, whereas dendritic cells elicit development of potentially pathogenic non-regulatory T cells capable of releasing pro-inflammatory mediators.
Complete understanding of the molecular mechanisms regulating this likely dynamic cooperation among accessory cell populations in the gut awaits further investigation.
Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses
Timothy L Denning, Yi-chong Wang, Seema R Patel, Ifor R Williams & Bali Pulendran
Published online: 16 September 2007 | doi 10.1038/ni1511
