New, interesting ways of controlling the immune system were published this week. The nose offers a new way to direct T cells to go to the gut and myeloid cells expressing the transcription factor Aire stop T helper cells in their tracks.
Intestinal Immunity via the Nose
Many mucosal immunologists have assumed that effector T cells in the gut must be stimulated exclusively by gut dendritic cells. A recent publication in the Journal of Experimental Medicine shows otherwise. In a publication by Ruane et al, it is shown that lung T cells, activated via antigens coming from the nose, express gut homing molecules and travel to the intestines. They were even able to vaccinate mice in this way against a common, intestinal pathogen. This opens up interesting possibilities not only for intestinally-directed vaccination via the nose, but also for the possible role of the respiratory tract in the development of intestinal inflammatory diseases.
New Ways to Control T Cells Are in the Aire
The most well known way that T helper cells are controlled is through regulatory T cells. Now, a new cell type is taking the stage: extrathymic Aire-expressing cells or eTACs. Aire is a transcription factor normally expressed by cells in the thymus and controls negative selection of young T cells by allowing the expression of self-antigens. The eTACs are described as being similar to an antigen-presenting cells with immature characteristics and are located in human lymphoid tissue. Upon antigen expression, antigen-specific T cells were functionally inactivated in a murine model of pancreatitis. The authors noted that these cells induced a robust tolerance that appeared to be resistant to external danger-signals, like pattern-recognition receptor stimulation. This could make these cells extremely useful for treating patients with chronic inflammatory diseases with known antigens.
Gardner, J. M., Metzger, T. C., McMahon, E. J., Au-Yeung, B. B., Krawisz, A. K., Lu, W., et al. (2013). Extrathymic Aire-Expressing CellsAre a Distinct Bone Marrow-Derived Population that Induce Functional Inactivation of CD4. Immunity, 1–13. doi:10.1016/j.immuni.2013.08.005
Ruane, D., Brane, L., Reis, B. S., Cheong, C., Poles, J., Do, Y., et al. (2013). Lung dendritic cells induce migration of protective T cells to the gastrointestinal tract. The Journal of experimental medicine, 210(9), 1871–1888. doi:10.1084/j