- 著者
- Ryota Sakai Kyoko Komai Mana Iizuka-koga Akihiko Yoshimura Minako Ito
- 出版者
- The Keio Journal of Medicine
- 雑誌
- The Keio Journal of Medicine (ISSN:00229717)
- 巻号頁・発行日
- pp.2019-0003-OA, (Released:2019-07-26)
- 参考文献数
- 143
- 被引用文献数
- 12
Inflammation and immune responses after tissue injury play pivotal roles in the resolution of inflammation, tissue recovery, fibrosis, and remodeling. Regulatory T cells (Tregs) are responsible for immune tolerance and are usually activated in secondary lymphatic tissues. Activated Tregs subsequently regulate effector T cell and dendritic cell activation. For clinical applications such as the suppression of both autoimmune diseases and the rejection of transplanted organs, methods to generate stabilized antigen-specific Tregs are required. For this purpose, transcriptional and epigenetic regulation of Foxp3 expression has been investigated. In addition to conventional Tregs, there are some Tregs that reside in tissues and are called tissue Tregs. Tissue Tregs exhibit tissue-specific functions that contribute to the maintenance of tissue homeostasis and repair. Such tissue Tregs could also be useful for Treg-based cell therapy. We recently discovered brain Tregs that accumulate in the brain during the chronic phase of ischemic brain injury. Brain Tregs resemble other tissue Tregs, but are unique in expressing neural cell-specific genes such as the serotonin receptor (Htr7); consequently, brain Tregs respond to serotonin. Here, we describe our experiences in the use of Tregs to suppress graft-versus-host disease and to promote neural recovery after stroke.
- 著者
- Akihiko Yoshimura
- 出版者
- The Keio Journal of Medicine
- 雑誌
- The Keio Journal of Medicine (ISSN:00229717)
- 巻号頁・発行日
- vol.58, no.2, pp.73-83, 2009-06-25 (Released:2009-07-17)
- 参考文献数
- 62
- 被引用文献数
- 27 78
Various cytokines are involved in the regulation of the immune system and of hematopoiesis. Most cytokines utilize the so-called JAK-STAT pathway, but others activate the Ras-ERK pathway, which is more important than the STAT pathway for the proliferation of hematopoietic cells. Dysregulation of cytokine signaling can cause a variety of diseases, including allergy, inflammation, and cancer. We have identified two important regulator families involved in cytokine signaling: the SOCS proteins and the Spred proteins. Suppressors of cytokine signaling (SOCS) proteins bind to JAK and to certain receptors, thereby suppressing further signaling events. Spred family proteins interact with Ras and Raf, thereby suppressing ERK activation. Studies have shown that SOCS and Spred proteins are key physiological regulators of immunity, hematopoiesis, and angiogenesis. Evidence is also emerging for the involvement of these proteins in human diseases.
- 著者
- Ryusuke Nakagawa Akihiko Yoshimura
- 出版者
- 日本炎症・再生医学会
- 雑誌
- Inflammation and Regeneration (ISSN:18809693)
- 巻号頁・発行日
- vol.35, no.3, pp.140-147, 2015 (Released:2015-06-19)
- 参考文献数
- 74
- 被引用文献数
- 1
The intestine, skin, and respiratory tract harbor pools of commensal microbes, known as microbiota. Over the last few years, the field of mucosal immunology has revealed that the microbiota play important roles in the host immune system. Here, we have summarized recent studies regarding the interaction between microbiota and the mucosal immune systems in health and diseases. The application of 16S rRNA PCR and new sequencing technology have enabled us to understand the composition of intestinal microbiota. Here, we specifically assess their contribution to obesity and cancer (chronic inflammatory conditions) as well as to inflammatory autoimmune diseases (e.g., inflammatory bowel disease and type 1 diabetes) and allergic syndromes. Optimization of the microbiota composition has been attempted via the intake of probiotic bacteria in various fermented foods and via fecal microbiota transplantation (FMT) from healthy donors to patients with Clostridium difficile-induced colitis. The presence of certain microbiota species affects the development and function of various types of immune cells, such as regulatory T (Treg) cells and interleukin-17-producing helper T (Th17) cells. Furthermore, innate lymphoid cells (ILCs) have also been shown to be regulated by microbiota. These findings indicate that manipulation of the microbiota could improve health and chronic diseases via immune regulation.