• マクロファージが組織に留まることによる慢性炎症を調節する。
  • 四日市喘息に関する気管支炎を研究する。





  • IL-4はマウスの体内で正常な生理発現と調節モードを持っている。
  • eGFPレポーター遺伝子はIL-4の発現を忠実に反映した。






  • 内因性のIL-4を発現するとともにこの機能を持っている:レポーター遺伝子を内因性IL-4遺伝子座の3'UTRに挿入する。
  • 挿入したシーケンスは調節される。
  • レポーター遺伝子はIL-4の発現を忠実に反映した。



  • eGFPの発現を監視することにより、IL-4を発現する細胞を直接検測することができる(図1)。
  • 免疫システムに影響しない:感染や攻撃に応じて完全なIL-4を生成することができる(図2)。
  • Th2細胞の移動と細胞の選別をよく監視できる。


Figure1. eGFP expression correlates with IL-4-expressing T cells and reflects IL-4 production

Figure1. eGFP expression correlates with IL-4-expressing T cells and reflects IL-4 production.

A) In contrast to Th1 conditions, the Th2-specific conditions on a 4get cell's eGFP- population, leads to a great increase expression of eGFP, reflecting IL-4 production. Purified, naive CD4+ eGFP- homozygous 4get T cells were labeled with PKH26 red fluor. Cells were cultured under Th1, neutral, or Th2 conditions in the presence of antigen-presenting cells and analyzed on day 4, after gating on CD4+ cells.

B) Only under Th2 conditions did 4get cells specifically express IL-4. Splenocytes from wild-type (+/+, open bars) and heterozygous (+/4get, hatched bars) or homozygous (4get/4get, dark bars) 4get mice were depleted of CD8+ cells by complement lysis and stimulated under Th1 or Th2 conditions for 5 days. Cells were washed and re-stimulated and supernatants were collected after 48 hours and analyzed for IL-4 and IFN-γ by ELISA.


Figure2. 4get cells retain the capacity to respond to N. brasiliensis infection in vivo by producing huge amount of IL-4. Homozygous 4get mice were infected with N. brasiliensis.
FACS analysis of lung, mesenteric lymph nodes (MLN), peripheral lymph nodes (PLN), and spleen (SPL) was performed after 10 days. Cells from the forward- and sidescatter lymphocyte gate were examined for CD4 and eGFP expression.



1. Mohrs M; Shinkai K; Mohrs K; Locksley RM.2001. Analysis of type 2 immunity in vivo with a bicistronic IL-4 reporter. Immunity 15(2):303-11.

2. Sofi MH; Qiao Y; Ansel KM; Kubo M; Chang CH.2011. Induction and Maintenance of IL-4 Expression Are Regulated Differently by the 3' Enhancer in CD4 T Cells. J Immunol 186(5):2792-9.

3. Wu D; Molofsky AB; Liang HE; Ricardo-Gonzalez RR; Jouihan HA; Bando JK; Chawla A; Locksley RM.2011.Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332(6026):243-7.



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