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A groundbreaking study led by researchers from Mass General Brigham, including experts from Brigham and Women’s Hospital, Massachusetts General Hospital, and Mass Eye and Ear, has shed light on the underlying mechanisms of allergic diseases, potentially paving the way for more effective therapies. The findings, published in Nature Immunology, unveil a previously unrecognized subset of immune cells implicated in chronic allergic reactions.
Allergic diseases, such as asthma, atopic dermatitis, and ulcerative colitis, afflict millions worldwide, necessitating lifelong treatments that often offer limited relief. Central to these conditions are T helper 2 (Th2) cells, which orchestrate the body’s immune response, particularly in allergic reactions. However, the sustained activity of Th2 cells in the presence of constant antigen exposure has long perplexed scientists.
The research team delved into the diversity and cellular mechanisms of human Th2 cells by analyzing gene expression in inflamed tissues from patients with nine different chronic allergic diseases. Through this comprehensive approach, they identified a subset of Th2 cells termed Th2-multipotent progenitor (Th2-MPP) cells.
Distinctive for their chronic expression of two transcription factors, TCF7 and LEF1, Th2-MPP cells exhibit characteristics akin to stem cells found in cancer and chronic infection. This suggests that they act as progenitor cells capable of giving rise to various types of cells implicated in disease pathology.
Further investigations, particularly focusing on nasal tissue from patients with chronic rhinosinusitis, revealed that Th2-MPP cells could serve as precursors for multiple types of Th2 cells responsible for disease symptoms.
Senior author Patrick Brennan, MD, PhD, from the Brigham Division of Allergy and Clinical Immunology, emphasized the potential of these findings for future therapeutic approaches. “We still have much to learn about the contribution of progenitor cells to chronic human inflammation, but we are hopeful that the study of this area of immunity could provide opportunities for future disease-modifying therapeutic approaches,” he said.
Lead author Radomir Kratchmarov, MD, a research fellow in the Brigham Division of Allergy and Clinical Immunology, underscored the significance of their work. “Our work suggests that Th2-MPP cells have the potential to sustain type 2 inflammation in the face of chronic antigen exposure and lays the foundation for further investigation to better understand their contribution to disease,” he explained.
These findings offer a promising avenue for the development of targeted therapies that address the root causes of allergic diseases, potentially offering relief to millions of patients worldwide. As researchers continue to unravel the complexities of immune responses, the prospect of more effective and tailored treatments for allergic diseases looms on the horizon.
Related Topics: Health & Medicine, Stem Cells, Immune System, Allergy
Related Terms: Gene Therapy, Stem Cell, T Cell, Natural Killer Cell
