単細胞ゲノミクスは,Th17細胞の病原性の重要なレギュレータを明らかにする
Jellert T Gaublomme1, Nir Yosef2, Youjin Lee3
1Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA; Department of Physics, Harvard University, 17 Oxford Street, Cambridge, MA 02138, USA.
Cell
|November 27, 2015
まとめ
自己免疫性脳内炎 (EAE) のTヘルパー17 (Th17) 細胞の異質性を調べると,病原性の分子要因が明らかになる. この細胞の多様性は 有害なTh17細胞を抑制し 有益なTh17細胞を保存する 標的型治療を導くことができます
科学分野:
- 免疫学
- ゲノミクス
- 神経科学
背景:
- Tヘルパー17 (Th17) 細胞のような免疫細胞サブタイプは,ゲノムレベルで完全に理解されていない重要な異質性を表しています.
- この細胞の多様性を理解することは 自己免疫疾患における免疫反応の解剖に不可欠です
研究 の 目的:
- Th17細胞の異質性や病原性に基づく分子メカニズムを調査する.
- Th17細胞の病原性および自己免疫性脳内炎 (EAE) の疾患感受性に関連した遺伝子を特定する.
主な方法:
- 中枢神経系 (CNS) とリンパ節 (LN) のTh17細胞をEAE中に分析するために,単細胞RNA配列化 (scRNA-seq) が使用された.
- また,Th17細胞は,病原性および非病原性条件下でインビトロで分化されました.
- 細胞状態をマッピングし,重要な遺伝子を特定するために,インビヴォおよびインビトロデータを統合した計算分析.
- 遺伝子機能はノックアウトマウスモデルを用いて検証された.
主要な成果:
- scRNA- seqは,Th17集団内の細胞状態のスペクトルを明らかにし,in vivoの異質性をin vitroの微分化条件と関連付けました.
- Th17細胞の病原性およびEAEに対する感受性を制御する重要な遺伝子が特定されました.
- 4つの新しい遺伝子 (Gpr65,Plzp,Toso,Cd5l) がTh17細胞機能と自己免疫性における役割について検証された.
結論:
- Th17細胞の細胞異質性は,EAEのような自己免疫環境におけるその機能に大きな影響を与えます.
- 特定された分子ドライバは,病原性Th17細胞の選択的抑制に関する洞察を提供します.
- このアプローチは,非病原性で組織を保護するTh17細胞を節約する標的治療を開発する可能性を秘めています.
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