Precocious Interleukin 21 Expression in Naive Mice Identifies a Natural Helper Cell Population in Autoimmune Disease

Autor: Gregory J. Christianson, Gregory W. Carter, Thomas J. Sproule, Theodore Duffy, Giljun Park, Shweta Jain, Derry C. Roopenian, Herbert C. Morse, Xu-Long Wang, Hongsheng Wang, Sarah Kate Lane-Reticker, Elisabeth A. Marnik
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Cell Reports, Vol 21, Iss 1, Pp 208-221 (2017)
ISSN: 2211-1247
Popis: Summary 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 (T FH ) 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)T H 21 cells, exhibits considerable similarity to mature T FH cells. nT H 21 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 + T REG cells. nT H 21 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.
Databáze: OpenAIRE