IL23 differentially regulates the Th1/Th17 balance in ulcerative colitis and Crohn’s disease

ABSTRACT Background: A novel T helper (Th) cell lineage, Th17, that exclusively produces the proinflammatory cytokine interleukin 17 (IL17) has been reported to play important roles in various inflammatory diseases. IL23 is also focused upon for its potential to promote Th17. Here, the roles of the IL23/IL17 axis in inflammatory bowel diseases such as ulcerative colitis (UC) and Crohn's disease (CD) were investigated. Methods: Mucosal samples were obtained from surgically resected specimens (controls, n = 12; UC, n = 17; CD, n = 22). IL17 production by isolated peripheral blood (PB) and lamina propria (LP) CD4 + cells was examined. Quantitative PCR amplification was performed to determine the mRNA expression levels of IL17, interferon c (IFNc), IL23 receptor (IL23R) and retinoic acid-related orphan receptor c (RORC) in LP CD4 + cells, and IL12 family members, such as IL12p40, IL12p35 and IL23p19, in whole mucosal specimens. The effects of exogenous IL23 on IL17 production by LP CD4 + cells were also examined. Results: IL17 production was higher in LP CD4 + cells than in PB. Significant IL17 mRNA upregulation in LP CD4 + cells was found in UC, while IFNc was increased in CD. IL23R and RORC were upregulated in LP CD4 + cells isolated from both UC and CD. IL17 production was significantly increased by IL23 in LP CD4 + cells from UC but not CD. Upregulated IL23p19 mRNA expression was correlated with IL17 in UC and IFNc in CD. Conclusions: IL23 may play important roles in controlling the differential Th1/Th17 balance in both UC and CD, although Th17 cells may exist in both diseases. Crohn's disease (CD) and ulcerative colitis (UC) are the two major forms of inflammatory bowel disease (IBD). Although the aetiology of IBD remains unclear, accumulating evidence suggests that dysfunction of the mucosal immune system plays important roles in IBD pathogenesis

Ancient Jomon genome sequence analysis sheds light on migration patterns of early East Asian populations

Funder: The excavation of the Ikawazu Jomon individual was supported by Grant-in-Aid for Scientific Research (B) (25284157) to YY. The Ikawazu Jomon genome project was organized by HI, and TH & HO who were supported by MEXT KAKENHI Grant Numbers 16H06408 and 17H05132, by Grant-in-Aid for Scientific Research on Innovative Areas (Cultural History of Paleoasia), and by Grant-in-Aid for Challenging Exploratory Research (23657167) and for Scientific Research (B) (17H03738). The Ikawazu Jomon genome sequencing was supported by JSPS KAKENHI Grant Number 16H06279 to ATo, and partly supported in the CHOZEN project in Kanazawa University, and in the Cooperative Research Project Program of the Medical Institute of Bioregulation, Kyushu University. Computations for the Ikawazu Jomon genome were partially performed on the NIG supercomputer at ROIS National Institute of Genetics.Abstract: Anatomically modern humans reached East Asia more than 40,000 years ago. However, key questions still remain unanswered with regard to the route(s) and the number of wave(s) in the dispersal into East Eurasia. Ancient genomes at the edge of the region may elucidate a more detailed picture of the peopling of East Eurasia. Here, we analyze the whole-genome sequence of a 2,500-year-old individual (IK002) from the main-island of Japan that is characterized with a typical Jomon culture. The phylogenetic analyses support multiple waves of migration, with IK002 forming a basal lineage to the East and Northeast Asian genomes examined, likely representing some of the earliest-wave migrants who went north from Southeast Asia to East Asia. Furthermore, IK002 shows strong genetic affinity with the indigenous Taiwan aborigines, which may support a coastal route of the Jomon-ancestry migration. This study highlights the power of ancient genomics to provide new insights into the complex history of human migration into East Eurasia