Coinhibitory Molecules in Autoimmune Diseases
CLINICAL & DEVELOPMENTAL IMMUNOLOGY
Authors: Watanabe, Norihiko; Nakajima, Hiroshi
Abstract
Coinhibitory molecules such as CTLA-4, PD-1 and BTLA negatively regulate immune responses. Multiple studies indicate that the deficiency ormutation of coinhibitorymolecules leads to the development of autoimmune diseases in mice and humans, indicating that the negative signals from coinhibitory molecules are crucial for the prevention of autoimmunity. In some conditions, the administration of decoy coinhibitory receptors (e. g., CTLA-4 Ig) or mAb against coinhibitory molecules suppresses the responses of self-reactive T cells in autoimmune diseases. Therefore, modulation of coinhibitory signals seems to be an attractive approach to induce tolerance in autoimmune diseases in humans where the disease-inducing self-antigens are not known. Particularly, administration of CTLA-4 Ig has shown great promise in animal models of autoimmune diseases and has been gaining increasing attention in clinical investigation in several autoimmune diseases in humans.
Screening for signatures of selection of Tianzhu white yak using genome-wide re-sequencing
ANIMAL GENETICS
Authors: Guangxin, E.; Yang, B-G; Basang, W-D; Zhu, Y-B; An, T-W; Luo, X-L
Abstract
The Tianzhu white yak, a domestic yak indigenous to the Qilian Mountains, migrated inland from the Qinghai-Tibet Plateau. Specific ecological and long-term artificial selection influenced the evolution of its pure white coat and physiological characteristics. Therefore, it is not only a natural population that represents a genomic selective region of environmental adaptability but is also an animal model for studying the pigmentation of the yak coat. A total of 24 261 829 variants, including 22 445 252 SNPs, were obtained from 29 yaks by genome-wide re-sequencing. According to the results of a selective sweep analysis of Tianzhu white yak in comparison to Tibetan yaks, nine candidate genes under selection in Tianzhu white yak were identified by combining pi, Tajima's D, pi A/pi B and F-ST statistics, with threshold standards of 5%. These genes include PDCD1, NUP210, ABCG8, NEU4, LOC102287650, D2HGDH, COL4A1, RTP5 and HDAC11. Five of the nine genes were classified into 12 molecular signaling pathways, and most of these signaling pathways are involved in environmental information processing, organismal systems and metabolism. A majority of these genes has not been implicated in previous studies of yak coat color and high-altitude animals. Our findings are helpful not only for explaining the molecular mechanism of yak coat pigmentation but also for exploring the genetic changes in Tianzhu white yak due to environmental adaptation.