We have previously demonstrated that upregulation of Sonic hedgehog (SHH) expression in allergic airway epithelia essentially contributes to the goblet cell metaplasia and mucous hypersecretion. However, the mechanism underlying the upregulation of SHH expression remains completely unknown. In cultured human airway epithelial cells, IL-4/IL-13 but not IL-5 robustly induces the mRNA and protein expression of SHH and in turn activates SHH signaling by promoting the JAK/STAT6-controlling transcription of SHH gene. Moreover, intratracheal instillation of IL-4 and/or IL-13 robustly activates STAT6 and concomitantly upregulates SHH expression in mouse airway epithelia, whereas, in Club cell 10-kDa protein (CC10)-positive airway epithelial cells of children with asthma, activated STAT6 closely correlates with the increased expression of SHH and high activity of SHH signaling. Finally, intratracheal inhibition of STAT6 by AS-1517499 significantly diminished the allergen-induced upregulation of SHH expression, goblet cell phenotypes, and airway hyperresponsiveness, in an ovalbumin- or house dust mite-induced mouse model with allergic airway inflammation,. Together, upregulation of SHH expression by IL-4/IL-13-induced JAK/STAT6 signaling contributes to allergic airway epithelial remodeling, and this study thus provides insight into how morphogen signaling is coordinated with Th2 cytokine pathways to regulate tissue remodeling in chronic airway diseases.

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Major histocompatibility complex (MHC) II deficiency is a rare primary immunodeficiency disorder which is characterized by the deficiency of MHC class II molecules. The disease is caused by transcription factor mutations including class II transactivator (CIITA), regulatory factor X-5 (RFX5), RFX associated protein (RFXAP) and RFXAP containing ankyrin repeat (RFXANK), respectively. Mutations in the RFXANK gene account for more than 70% of all known patients worldwide. Herein, we reported a 10-month-old boy with MHC II deficiency caused by a novel mutation in RFXANK gene (c.337+1G>C) The boy was admitted to the hospital due to pneumonia and diarrhea at four months of age. Genetic analysis revealed a novel homozygous mutation in the RFXANK gene which derived from the c.337+1G>C heterozygous mutations in the RFXANK gene of his parents. The boy died 3 months after the diagnosis. More than 200 cases have been reported; and literature review revealed different mutation rates of four transcription factors in different countries or regions. This is the first case report of MHC II deficiency from East Asia. We also described all gene mutations which causing MHC II deficiency and epidemiology of MHC II deficiency with gene mutations in this paper.