Precocious Interleukin 21 Expression in Naive Mice Identifies a Natural Helper Cell Population in Autoimmune Disease.
Document Type
Article
Publication Date
10-3-2017
JAX Source
Cell Rep 2017 Oct 3; 21(1):208-221.
Volume
21
Issue
1
First Page
208
Last Page
221
ISSN
2211-1247
PMID
28978474
DOI
https://doi.org/10.1016/j.celrep.2017.09.036
Abstract
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. Cell Rep 2017 Oct 3; 21(1):208-221.
Recommended Citation
Marnik E,
Wang X,
Sproule TJ,
Park G,
Christianson GJ,
Lane-Reticker S,
Jain S,
Duffy T,
Wang H,
Carter GW,
Morse H,
Roopenian DC.
Precocious Interleukin 21 Expression in Naive Mice Identifies a Natural Helper Cell Population in Autoimmune Disease. Cell Rep 2017 Oct 3; 21(1):208-221.