Interleukin-27 (IL-27) suppresses immune responses through inhibition of the development of IL-17 producing Th17 cells and induction of IL-10 production.We previously showed that forced expression of early growth response gene 2 (Egr-2), a transcription factor required for T-cell anergy induction, induces IL-10 and lymphocyte activation gene 3 expression and confers regulatory activity on CD4 + T cells in vivo. Here, we evaluated the role of Egr-2 in IL-27-induced IL-10 production. Among various IL-10-inducing factors, only IL-27 induced high levels of Egr-2 and lymphocyte activation gene 3 expression. Intriguingly, IL-27 failed to induce IL-10 in Egr-2-deficient T cells. IL-27-mediated induction of Prdm1 that codes B lymphocyte induced maturation protein-1, a transcriptional regulator important for IL-10 production in CD4 + T cells, was also impaired in the absence of Egr-2. Although IL-27-mediated IL-10 induction was dependent on both STAT1 and STAT3, only STAT3 was required for IL-27-mediated Egr-2 induction. These results suggest that IL-27 signal transduction through Egr-2 and B lymphocyte induced maturation protein-1 plays an important role in IL-10 production. Furthermore, Egr-2-deficient CD4 + T cells showed dysregulated production of IFN-γ and IL-17 in response to IL-27 stimulation. Therefore, Egr-2 may play key roles in controlling the balance between regulatory and effector cytokines.Keywords: Blimp-1 r Egr-2 r IL-10 r IL-27 r inducible regulatory T (Treg) cells r Prdm1 See accompanying Commentary by Vasanthakumar and KalliesAdditional supporting information may be found in the online version of this article at the publisher's web-site [3,4]. IL-10 is an anti-inflammatory cytokine which was initially described as a cytokine associated with Th2 cells that inhibits the production of IFN-γ by Th1 cells [5,6]. A number of reports have revealed that IL-10 suppresses cytokine production and proliferation of T cells [7,8] and inhibits the T-cell-stimulating capacity of APCs [9]. IL-10-deficient mice die with spontaneously developed inflammatory bowel disease [10].Interleukin-27 (IL-27), a member of the IL-12/IL-23 heterodimeric family of cytokines produced by APCs, is composed of two chains, p28 and EBV-induced gene 3 [11]. IL-27 induces the expansion of Th1 cells by activating the STAT1-mediated T-bet pathway [12], but IL-27Rα-deficient mice developed severe EAE with enhanced Th17-cell responses [13]. The immunosuppressive effects of IL-27 depend on inhibition of the development of Th17 cells and induction of IL-10 production [14]. Recently, IL-27 has been identified as a differentiation factor for IL-10-producing Tr1 cells [15][16][17]. On the other hand, B lymphocyte induced maturation protein-1 (Blimp-1) (coded by Prdm1 gene), a zinc finger-containing transcriptional regulator that is well known to be a regulator of plasma cell differentiation, is also important for IL-10 production in naïve CD4 + T cells. Martins et al. [18,19] reported that Blimp-1-deficient CD4 + T cells proliferated more and produce...
Eight patients underwent hemihypoglossal-facial nerve anastomosis (anastomosis of a split hypoglossal nerve to the facial nerve) for treatment of unilateral facial palsy. All patients previously had undergone resection of a large acoustic neurinoma and the facial nerve had been resected at that time. The interval between tumor resection and hemihypoglossal-facial nerve anastomosis ranged from 1 to 6 months, with an average of 2.1 months. Postoperative recovery of facial movement was good in all cases during an average follow-up period of 4.2 years. In all eight patients, the degree of hypoglossal nerve atrophy on the operated side was graded mild or moderate, but not severe. It was concluded that hemihypoglossal-facial nerve anastomosis results in good facial reanimation as long as the procedure is performed early after the onset of facial palsy and that this procedure may reduce the degree of hemiglossal atrophy in comparison with classic hypoglossal-facial nerve anastomosis.
The cephalic index is a method of assessing skull morphology in craniosynostosis. There are known racial differences; however, there are few reports on this index in Japan. In this study, we investigated the cephalic indices of Japanese children with normal brain development using axial slice computed tomography. Children presented to our institution because of head injuries but received no particular diagnosis. One hundred four children with normal brain development (62 males and 42 females) were divided into 7 age categories, namely, 4 categories for those younger than 1 year and 3 categories for those between 1 and 3 years. The cephalic index was calculated according to the following equation: (cephalic width/cephalic length) × 100. The cephalic indices by age groups were as follows: 86.7, 0 to 3 months (n = 21); 87.5, 4 to 6 months (n = 9); 89.2, 7 to 9 months (n = 16); 86.3, 10 to 12 months (n = 9); 85.9, 1 year (n = 25); 86.3, 2 years (n = 15); and 83.7, 3 years (n = 9). In this study, the cephalic indices of Japanese children with normal brain development tended to be more brachycephalic than those of white children, as reported by Haas and Waitzman. Thus, we formulated the classification of current cephalic indices of children with normal brain development in Japan.
Recent evidence supports the use of end-to-side neurorrhaphy for the treatment of certain peripheral nerve disorders. However, the mechanism by which nerves regenerate following this procedure is still unclear. To address this question, the authors designed a new end-to-side coaptation model in rats in which the donor nerves were uninjured. The regenerated axons at the coaptation site were observed directly using fluorescent dye as the neural tracer. The sciatic nerve from adult Wistar rats was transplanted between the left and right median nerves. Fifteen rats were divided into three groups. In group I, the donor (right median) nerve was sutured end to side to the divided grafted nerve using a noninjury technique. In group II, the aponeurosis of the spinal muscles was harvested and the sciatic and right median nerves were coapted end to side noninjuriously by wrapping them in the excised aponeurosis. In group III, a perineurial window was created and a partial neurectomy was carried out at the suture site, after which the sciatic and right median nerves were sutured end to side. Sixty days after the operation, nerve regeneration was evaluated by recording action potentials in the grafted nerve, by performing electromyography in the flexor muscles in the forearm, and by histological examination. The grafted nerves were fixed and sectioned, the number of regenerated nerve fibers was counted, and axonal diameters were measured. Fluorescent dye crystal was used, in conjunction with confocal microscopy, to observe the regenerated axons at the co-aptation site. The results showed that nerve regeneration had occurred in the animals, as determined electrophysiologically and histologically. Both the right and left flexor muscles of the forearm contracted simultaneously as a result of indirect electric stimulation of the grafted nerve, which suggests that the regenerated nerve was physiologically connected with the donor nerve. Nerve fiber counts did not show any differences among groups (p > 0.05), but axonal diameters were significantly greater in group III than in the other two groups. Fluorescent dye staining revealed the presence of regenerated nerve fibers beyond the coaptation site. In group III, the regenerating nerves were observed within the whole section of the coaptation site and collateral sprouting was found to occur even at a site distal to the suture. From these results, the authors conclude that in end-to-side neurorrhaphy, nerve regeneration occurs by collateral sprouting from the donor nerve.
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