Tertiary lymphoid tissues in the colon: friend and foe.

In mammals, a variety of different lymphoid tissues have evolved as an integral part of the immune system that allows the host to survive in a sometimes hostile environment. While the development of secondary lymphoid organs is programmed in the fetus, the induction of other lymphoid structures like isolated lymphoid follicles (ILFs) in the gut or tertiary lymphoid tissues (tLT) need additional external triggers after birth. It is well established that for the development of secondary lymphoid organs, as well as ILFs, RORgt expressing lymphoid tissue inducer (LTi) cells play an important role. Yet, the requirement of these cells for tLT induction, especially in the gut, was less clear. Here, I will discuss recent data demonstrating that RORgt expressing LTi cells are not required for the development of tLT in the colon. In contrast, such structures even develop spontaneously in the absence of RORgt. In RORgt (-/-) mice, this is part of the host's strategy to establish a viable homeostasis between the intestinal microbiota and the host, despite the loss of important components of the intestinal immune system in these mice. Although this highlights the amazing capacity of the immune system for adaptation, I will also discuss the adverse effects of such a compensatory immune mechanism for the host.