Cell Rep. 2017 Oct 3;21(1):208-221. doi: 10.1016/j.celrep.2017.09.036.
Marnik, EA; Wang, X; Sproule, TJ; Park, G; Christianson, GJ; Lane-Reticker, SK; Jain, S; Duffy, T; Wang, H; Carter, GW; 3rd, HC Morse; Roopenian, DC
The Jackson Laboratory, Bar Harbor, ME, USA. Tufts University, Boston, MA, USA. National Institute of Allergy and Infectious Disease (NIAID), NIH, Rockville, MD, USA.
Interleukin 21 (IL-21) plays key roles in humoral immunity and autoimmune diseases. It is known to function in mature CD4+ T follicular B cell helper (TFH) cells, but its potential involvement in early T cell ontogeny is unclear. Here, we find that a significant population of newly activated thymic and peripheral CD4+ T cells functionally expresses IL-21 soon after birth. This naturally occurring population, termed natural (n)TH21 cells, exhibits considerable similarity to mature TFH cells. nTH21 cells originating and activated in the thymus are strictly dependent on autoimmune regulator (AIRE) and express high levels of NUR77, consistent with a bias toward self-reactivity. Their activation/expansion in the periphery requires gut microbiota and is held in check by FoxP3+ TREG cells. nTH21 cells are the major thymic and peripheral populations of IL-21+ cells to expand in an IL-21-dependent humoral autoimmune disease. These studies link IL-21 to T cell ontogeny, self-reactivity, and humoral autoimmunity.
The team at Ozgene has over two decades of experience creating customised knockout and knock-in mice for pivotal medical research globally. Over 350 scientific publications are based on research using Ozgene mice.