Discoveries in Immunology
Link Discovered Between New Type of Cell and a Deadly Inflammatory Disorder
A research team led by BRI’s Jessica Hamerman, PhD, Member and Associate Director of Academic Affairs, made a discovery that lights the way to treat life-threatening complications of autoimmune and viral diseases.
“Our discovery demonstrates that if we interfere with the development of these iHPCs, we’ll be able to treat MAS as well as other dangerous forms of anemia,” Hamerman said.
The team’s discovery, published in the journal Science, could lead to new treatments for a deadly form of inflammation in children with systemic juvenile idiopathic arthritis (SJIA), malaria and Kawasaki disease, as well as patients with lupus.
Macrophage activation syndrome, or MAS, is an inflammatory condition that leads to anemia; people with MAS suffer persistent fevers, headaches, large lymph nodes and, in severe cases, organ dysfunction or death. The research team found a unique type of cell, which they termed “inflammatory hemophagocytes” (iHPCs), that eat red blood cells in MAS and malaria. They demonstrated that iHPCs develop under the influence of two specific proteins that recognize infection and are associated with autoimmune disease.
“Our discovery demonstrates that if we interfere with the development of these iHPCs, we’ll be able to treat MAS as well as other dangerous forms of anemia,” Hamerman said. “We can draw a parallel between autoimmune or viral associated MAS and malaria. The same signals cause iHPCs and anemia in these diseases. In both cases, the iHPCs are ‘eating’ red blood cells and destroying them.”
Dr. Hamerman said next steps will involve collaborations with pediatricians and pediatric rheumatologists to look for iHPCs in the blood of children with autoimmune disease-related anemia, as well as healthy individuals, with a goal of quickly identifying potential targets for treatments. Comparisons with blood samples infected by malaria are already under way, she said.
Watch Jessica Hamerman, PhD, explain her lab’s work to investigate iHPC in both MAS and blood stage malaria.
Skin Immune Cell Discovery Challenges Assumptions about T cells
BRI scientists scrutinized a newly identified population of human immune cells in the blood that appear to have everything in common with infection-fighting T cells isolated from the skin.
BRI Principal Investigator Daniel Campbell, PhD, in partnership with scientists at the University of Salzburg in Austria, the University of Pennsylvania and other research institutions, demonstrated that T cells that were previously assumed to stay in the skin, and are referred to as tissue-resident memory T cells, can exit skin tissue, enter the blood and circulate throughout the body. These T cells can then relocate into skin at other locations of the body.
In addition to potential implications for treatment of wounds and skin infections, the identification of this cell population presents an opportunity to identify therapies for immune-related diseases that affect the skin, including scleroderma, psoriasis and a form of lymphoma called mycosis fungoides.
“Immunologists have largely thought once cells like these went to the skin, they would be locked in place and stay there forever, but now we find some are capable of re-entering the bloodstream,” said Dr. Campbell, who also serves as director of BRI’s new Fundamental Immunology Center. “We think these migrating cells can use blood as a highway to spread immunity to different parts of the skin all over the body,” he said.
The findings, published in the journal Science Immunology, challenged previous beliefs that tissue-resident memory T cells are strictly retained in the tissue, in this case the skin. Further, the presence of a specific protein, CD69, appears to control whether these T cells are retained in the skin or migrate away.
By studying these T cells in more detail, the team found that the migration of the T cells likely plays a role in the healing of skin wounds and the ability to recognize and protect against infection. “Once these cells have battled an infectious agent at one site on the skin, they may be able to recognize and fend off infection at other sites and in subsequent encounters,” Dr. Campbell said.More Stories