Details

Autor(en) / Beteiligte

• Kang, Jung-Ah
• Park, Sang-Heon
• Jeong, Sang Phil
• Han, Min-Hee
• Lee, Cho-Rong
• Lee, Kwang Min
• Kim, Namhee
• Song, Mi-Ryoung
• Choi, Murim
• Ye, Michael
• Jung, Guhung
• Lee, Won-Woo
• Eom, Soo Hyun
• Park, Chul-Seung
• Park, Sung-Gyoo

Titel

Epigenetic regulation of Kcna3-encoding Kv1.3 potassium channel by cereblon contributes to regulation of CD4⁺ T-cell activation

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2016-08, Vol.113 (31), p.8771-8776

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• The role of cereblon (CRBN) in T cells is not well understood. We generated mice with a deletion in Crbn and found cereblon to be an important antagonist of T-cell activation. In mice lacking CRBN, CD4⁺ T cells show increased activation and IL-2 production on T-cell receptor stimulation, ultimately resulting in increased potassium flux and calcium-mediated signaling. CRBN restricts T-cell activation via epigenetic modification of Kcna3, which encodes the Kv1.3 potassium channel required for robust calcium influx in T cells. CRBN binds directly to conserved DNA elements adjacent to Kcna3 via a previously uncharacterized DNA-binding motif. Consequently, in the absence of CRBN, the expression of Kv1.3 is derepressed, resulting in increased Kv1.3 expression, potassium flux, and CD4⁺ T-cell hyperactivation. In addition, experimental autoimmune encephalomyelitis in T-cell–specific Crbn-deficient mice was exacerbated by increased T-cell activation via Kv1.3. Thus, CRBN limits CD4⁺ T-cell activation via epigenetic regulation of Kv1.3 expression.