Our bodies contain immune cells called "memory T cells" that remember viruses and bacteria that have invaded before and respond quickly and powerfully upon re-exposure. These cells act as guardians during infection, but their long-term persistence in the body also makes them a major cause of chronic inflammation—including that of allergic and autoimmune conditions such as hay fever, asthma, ulcerative colitis, and rheumatoid arthritis.
A research group led by Professor Kiyoshi Hirahara from the Graduate School of Medicine at Chiba University clarified the mechanism by which "CD4+ tissue-resident memory T cells (CD4+ TRM cells)," a type of immune cell, persist long-term in tissues such as the lungs and intestines following infection by pathogenic microorganisms. The group identified that the sustained production of inflammatory cytokines—secreted proteins that trigger inflammation—is regulated by a protein called hepatic leukemia factor (HLF), which controls how genes function. The group also found that mice lacking HLF showed a marked reduction in CD4+ TRM cell numbers, and that tissue hardening caused by inflammation and fibrosis was suppressed. They further showed that HLF directly controls both the factors responsible for anchoring these cells in tissue and the genes responsible for their exit from tissue, causing the cells to remain in tissue for an extended time. In addition, the group confirmed that in various human chronic inflammatory diseases, these HLF-responsive cells infiltrate the affected tissues.
These findings deepen our understanding of the pathology of chronic inflammatory conditions such as asthma and autoimmune diseases and are expected to lead to the development of new treatments. Going forward, clarifying how HLF is induced could open the door to clinical applications and drug discovery.
(Article: Masanori Nakajo)
