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Researchers identify novel sensory pathway that modulates pro-inflammatory cells

July 05, 2017

Because of their importance in infectious and autoimmune diseases, the proportion of Th17 cells in the blood of an individual has become a useful biomarker when evaluating autoimmune disease progression or patient responses to treatments. The current method to quantify Th17 cells in blood or tissues involves looking at the secretion of their characteristic cytokines (i.e., IL-17 or IL-22) directly after the cells have been isolated. However, the researchers in this study noticed that this type of "ex vivo" cytokine analysis underestimates the frequency of Th17 cells in the blood of both healthy individuals and rheumatoid arthritis patients. In fact, the majority of human Th17 cells in blood displayed a "poised" phenotype, expressing neither IL-17 nor IL-22 unless they were first stimulated with gamma-c cytokines. This finding has important implications, both for how T cells are classified based on cytokine expression, and how Th17 cells are enumerated in human clinical investigations.

"There are many published studies that have relied on counting human Th17 cells based on their ability to secrete IL-17 out of the blood. We will have to be more careful interpreting these results, since a significant portion of Th17 reserves are not detected by current assays," said Dr. Unutmaz.

The findings in this study also underscore the local tissue environment in modulating the function of T cells. The researchers speculate that the Th17 cells sense the micro-environment for signs of inflammation, which can be caused by bacterial infections, and accordingly decide how potently they should respond. However, if the inflammatory milieu is unregulated or triggered by self-antigens and sustained by local cells, Th17 cells can cause in responses that are either unwanted or not proportionate to the external insults. So manipulating the novel regulatory mechanisms discovered in this study could lead to more specific treatments that can fine-tune the imbalance of the immune responses.

"An immune response mediated by Th17 cells is dangerous like a double-edged sword, they can do more harm than good if not controlled. We now know what excites Th17 cells to be armed. If we can find drugs that can turn this pathway on and off, we could potentially induce them when needed and prevent their unwanted responses that results in autoimmune diseases," said Dr. Unutmaz.

Source: NYU Langone Medical Center / New York University School of Medicine