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Updated: Feb 20, 2026

Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 26, 2013
Cyclic AMP-Responsive Element-Binding Protein (CREB) is Critical in Autoimmunity by Promoting Th17 but Inhibiting
Xiaohu Wang1, Lu Ni1, Dehui Chang1
1Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China.
Abstract:
The molecular mechanisms that govern differential T cell development into pro-inflammatory Th17 vs. regulatory T (Treg) cells remain unclear. Here, we show that selective deletion of CREB in T cells or Th17 cells impaired Th17 cell differentiation in vitro and in vivo, and led to resistance to autoimmune diseases. Mechanistically, CREB, activated by CD3-PKC-ϴ signaling, plays a key role in regulating Th17 cell differentiation, at least in part through directly binding to the Il17-Il17f gene locus. Unexpectedly, although dispensable for FOXP3 expression and for the homeostasis and suppressive function of thymus-derived Treg cells, CREB negatively regulates the survival of TGF-β-induced Treg cells, and deletion of CREB resulted in increased FOXP3+ Treg cells in the intestine and protection in a colitis model. Thus, CREB is critical in autoimmune diseases by promoting Th17 cell and inhibiting de novo Treg cell generation.
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