A study published on January 9 in PNAS reveals how DCIR, a receptor expressed by dendritic cells, regulates immunity to tuberculosis. These results will allow the development of DCIR-targeting compounds to modulate immunity and inflammation during treatment of tuberculosis (TB) and other inflammatory disorders.
Dendritic cells are immune cells, whose main function is to stimulate the differentiation of lymphocytes in lymphoid organs. During TB, dendritic cells activate, through the production of interleukin (IL)-12, T helper 1 (Th1) lymphocytes, which produce gamma interferon. Gamma interferon activates macrophages to control the TB bacillus. Thus, Th1 cells are required for protection against TB, yet their uncontrolled activation leads to inflammatory destruction of the lung tissue.The scientists discovered that a protein expressed in dendritic cells, DCIR, is required for controlling IL-12 production and Th1 differentiation by sustaining type I interferon signaling, which inhibits IL-12 synthesis. DCIR-deficient dendritic cells are impaired in responding to type I interferon, produce more IL-12 and induce an increased differentiation of Th1 cells.
Thus DCIR-deficient mice develop more Th1 cells upon infection by the TB bacillus, leading to a better control of the pathogen but also to an increased inflammation in the lung. This result was generalized beyond TB using a model of vaccination with ovalbumin, a model antigen.
One can envisage that DCIR-targeting small compounds might be used to stimulate or refrain Th1 cell activation in TB and other infectious and non-infectious diseases. These results might explain why DCIR-deficient mice develop more autoimmune disorders, such as experimental auto-encephalitis, a model of multiple sclerosis, or aging-associated bone degradation. Manipulating DCIR activity might be useful in the context of these diseases.
The information on INSB website (in french)
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