Airing Oneself

See allHide authors and affiliations

Science  21 Nov 2003:
Vol. 302, Issue 5649, pp. 1295-1297
DOI: 10.1126/science.302.5649.1295e

As a means of avoiding autoimmunity, most T cells that are capable of recognizing self-proteins are deleted as they develop within the thymus. However, this presents the conundrum of how these thymocytes become exposed to self-proteins in the first place, because many of these proteins should be restricted to tissues outside of the thymus, such as the pancreas. Part of the solution was provided recently by the finding that the transcriptional regulator Aire drives ectopic expression of tissue-specific genes in the thymic epithelium.

In looking for how Aire itself might be regulated, Chin et al. explored the observation that mice lacking the cytokine lymphotoxin-α (LTα) or its receptor LTγR manifest autoimmune characteristics similar to those of mice that don't have the Aire gene. Presumably as a consequence of reduced ectopic gene expression, mice deficient in either LTγR or LTα generated autoantibodies and self-reactive lymphocytes that then induced pathology in a variety of tissues. Aire expression was considerably reduced in the thymic epithelium of both LTγR- and LTα-deficient mice but could be enhanced in the latter set of mice by administering an antibody that acted as an LTγR agonist. Restoration of Aire expression via LTγR signaling also enhanced the thymic expression of insulin, which is one of the genes under control of Aire. Because LTα is expressed after thymocyte activation, developing T cells may influence their own survival through modulation of Aire expression. — SJS

Nature Immunol. 4, 1121 (2003).

Navigate This Article