Ror t+ Innate Lymphoid Cells in Intestinal Homeostasis and Immunity

Innate lymphoid cells (ILC) combine innate and adaptive immune functions and are part of the first line of defense against mucosal infections. ILC are set apart from adaptive lymphocytes by their independence on RAG genes and the resulting absence of specific antigen receptors. In this review, we will discuss the biology and function of intestinal ILC that express the nuclear hormone receptor Ror t (encoded by the Rorc gene) and highlight their role in intestinal homeostasis and immunity. Copyright © 2011 S. Karger AG, Basel Ror t+ Innate Lymphoid Cells Expression of Ror t delineates a heterogeneous group of ILC that depend on RORC and the helix-loop-helix protein ID2 for their development [1–7] . Ror t+ ILC have a variety of phenotypes that might represent either activation states or progressive developmental intermediates of one cell lineage, or distinct lineages of Ror t+ ILC that share a common precursor. In the fetal murine intestine the predominant ILC population is characterized by expression of CD117 (ckit) and CD127 (IL7R ) [8, 9] . The majority of these Ror t+ ILC express CD4 and were previously termed lymphoid tissue inducer (LTi) cells because of their Received: March 29, 2011 Accepted after revision: June 27, 2011 Published online: September 5, 2011 Journal of Innate Immunity Dr. T. Cupedo Department of Hematology, Room Ee1330f Erasmus University Medical Center PO Box 2040, NL–3000 CA Rotterdam (The Netherlands) Tel. +31 10 704 4082, E-Mail t.cupedo @ erasmusmc.nl © 2011 S. Karger AG, Basel 1662–811X/11/0036–0577$38.00/0 Accessible online at: www.karger.com/jin Aparicio-Domingo/Cupedo J Innate Immun 2011;3:577–584 578 Ror t expression, and without conversion into conventional NK cells [17] . ILC display several features normally associated with activated cells of the adaptive immune system. Similar to activated T and B cells, ILC express surface lymphotoxin1 2 (LT) and can secrete TNFand IL-2 [21, 22] . In addition, ILC produce cytokines normally secreted by specific T helper cells. In both humans and mice, ILC can secrete IL-22 and IL-17a, reminiscent of T helper 17 cells [11–15, 21, 23, 24] . The main difference between adaptive immune cells and ILC is that the latter do not have a specific antigen receptor, and as a consequence will be activated in a non-antigen-specific manner. The production of effector molecules associated with adaptive immunity, but without the antigen restriction, endows ILC with the ability to respond much quicker than adaptive cells, but also to function in an environment in which activating signals for adaptive cells are lacking. A prime example of this is the developing mammalian embryo. Lymphoid Organogenesis in the Intestine: