Plant homeodomain finger protein 11 promotes class switch recombination to IgE in murine activated B cells. Issue 2 (29th November 2013)

• Record Type: Journal Article
• Authors: Ikari, J.; Inamine, A.; Yamamoto, T.; Watanabe‐Takano, H.; Yoshida, N.; Fujimura, L.; Taniguchi, T.; Sakamoto, A.; Hatano, M.; Tatsumi, K.; Tokuhisa, T.; Arima, M.
• Is Part Of: Allergy. Volume 69:Issue 2(2014:Feb.)
• Page Start: 223
• Page End: 230
• Publication Date: 2013-11-29
• Subjects: Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.12328
• Languages: English
• ISSNs: 0105-4538

Abstract

<abstract abstract-type="main" id="all12328-abs-0001"> <title>Abstract</title> <sec id="all12328-sec-0001" sec-type="section"> <title>Background</title> <p>Polymorphisms of the <italic>Plant homeodomain finger protein 11</italic> (<italic>PHF11</italic>) are strongly associated with high serum IgE levels and clinical severity of atopic patients. However, the precise mechanism has not been fully elucidated. We investigated the role of Phf11 in class switch recombination (CSR) to IgE by activated B cells.</p> </sec> <sec id="all12328-sec-0002" sec-type="section"> <title>Methods</title> <p>We generated Phf11 transgenic (Lckd‐Phf11‐Tg) mice that express the exogenous murine Phf11 in lymphocytes under the control of distal Lck promoter. We examined IL‐4‐induced CSR to IgE in activated Lckd‐Phf11‐Tg B cells <italic>in vitro</italic>. We analyzed production of ovalbumin (OVA)‐specific IgE and nose‐scratching symptoms in Lckd‐Phf11‐Tg mice using an OVA‐induced allergic rhinitis model.</p> </sec> <sec id="all12328-sec-0003" sec-type="section"> <title>Results</title> <p>The exogenous Phf11 promoted CSR to IgG1 and IgE in activated B cells with an increase in germ line transcript (<italic>GLT</italic>) γ<sub><italic>1</italic></sub> and <italic>GLT</italic> ε expression. The exogenous Phf11 augmented transcriptional activity of the <italic>GLT</italic> γ<sub><italic>1</italic></sub> and <italic>GLT</italic> ε promoters through permissive histone modifications and binding of NF‐κB and STAT6. Furthermore, the exogenous Phf11 bound to the <italic>GLT</italic> ε promoter with increased binding of NF‐κB. Silencing of the endogenous Phf11 reduced the frequency of CSR to IgE and <italic>GLT</italic> ε expression, but not to IgG1 or <italic>GLT</italic> γ<sub><italic>1</italic></sub> expression, in activated B cells. In an allergic rhinitis model, Lckd‐Phf11‐Tg mice showed a significant increase in the production of OVA‐specific IgE and the frequency of nose scratching.</p> </sec> <sec id="all12328-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Phf11 accelerates CSR to IgE in activated B cells by increasing the transcriptional activity of <italic>GLT</italic> ε promoter and contributes to the exacerbation of allergic responses. These findings provide a novel therapeutic target for allergic diseases.</p> </sec> </abstract>