Lungs and Aire Offer New T Cell Control

Nimm dich selbst by der Nase
The nose may be a crucial player in initiating intestinal immunity.
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.

References

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

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