Smad2/3 and IRF4 play a cooperative role in IL-9-producing T cell induction.

IL-9 is a pleiotropic cytokine that can regulate autoimmune and allergic responses. Th9 cells can develop from naive T cells or Th2 cells through stimulation by TGF-ß in vitro. In this study, we demonstrated that Smad2 and Smad3 are necessary for IL-9 production from T cells in an OVA-induced asthma model using T cell-specific Smad2- and Smad3-deficient mice. Smad2 and Smad3 were also redundantly essential for TGF-ß signaling to induce histone modifications for Il9 transcription. Although Smad2/3 was recruited to the Il9 promoter by TGF-ß stimulation, they are not sufficient to activate the Il9 promoter. By the screening the transcription factors, we found that IFN regulatory factor 4 (IRF4) was essential for the Smad2/3-mediated Il9 promoter activation. In addition, Smad2/3 physically interacted with IRF4, and Smad2/3 did not bind to the Il9 promoter and could not induce Th9 in IRF4-deficient T cells. Similarly, IRF4 could not stimulate Il9 transcription in the absence of Smad2/3, and TGF-ß enhanced IRF4 recruitment to the Il9 promoter in a Smad2/3-dependent manner. We propose that Smad2/3 and IRF4 cooperatively transactivate the Il9 promoter and play an important role in regulating allergic immune responses by inducing Th9 cells.

17-year Follow-up after Mandibular Distraction Performed in an Infant with Robin Sequence.

Robin sequence is a congenital anomaly, first described by Pierre Robin as a triad of micrognathia, upper airway obstruction and glossoptosis. The most significant airway management technique is the use of distraction osteogenesis to advance the mandible. On the other hand, late complications such as permanent dentition loss and malformation of the damaged teeth have been reported. Therefore, long-term follow-up after mandibular distraction is important. In our case report, we describe 17 years of follow-up after mandibular distraction performed in a 4-month-old male infant with Robin sequence. The patient was a male with a cleft palate. The tracheotomy and tongue-lip adhesion was performed 1 month after birth, because the percutaneous oxygen saturation decreased to 70% during feeding and crying. However, postoperative X-ray examination revealed that he could not obtain sufficient airway after the operation. For the purpose of closing the tracheotomy early, we performed bilateral mandibular distraction at the age of 4 months. The bilateral corticotomy was performed on the mandibular body and an internal traction device was placed. The mandible was bilaterally lengthened by 17.5 mm, and expansion of the airway was confirmed by X-ray. A cleft palate operation was performed at the age of 17 months. At the age of 3 years, the tracheostomy orifice closed and speech/language training and orthodontics were begun. Dental panoramic radiographs showed favorable mandibular growth. No additional operation has been performed. Finally, his orthodontic treatment was completed without any complications at age 17.