Yasumasa Nishito
Institute of Medical Science
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Publication
Featured researches published by Yasumasa Nishito.
Nature Immunology | 2013
Yoshitaka Taketomi; Noriko Ueno; Takumi Kojima; Hiroyasu Sato; Remi Murase; Kei Yamamoto; Satoshi Tanaka; Mariko Sakanaka; Masanori Nakamura; Yasumasa Nishito; Momoko Kawana; Naotomo Kambe; Kazutaka Ikeda; Ryo Taguchi; Satoshi Nakamizo; Kenji Kabashima; Michael H. Gelb; Makoto Arita; Takehiko Yokomizo; Motonao Nakamura; Kikuko Watanabe; Hiroyuki Hirai; Masataka Nakamura; Yoshimichi Okayama; Chisei Ra; Kosuke Aritake; Yoshihiro Urade; Kazushi Morimoto; Yukihiko Sugimoto; Takao Shimizu
Microenvironment-based alterations in phenotypes of mast cells influence the susceptibility to anaphylaxis, yet the mechanisms underlying proper maturation of mast cells toward an anaphylaxis-sensitive phenotype are incompletely understood. Here we report that PLA2G3, a mammalian homolog of anaphylactic bee venom phospholipase A2, regulates this process. PLA2G3 secreted from mast cells is coupled with fibroblastic lipocalin-type PGD2 synthase (L-PGDS) to provide PGD2, which facilitates mast-cell maturation via PGD2 receptor DP1. Mice lacking PLA2G3, L-PGDS or DP1, mast cell–deficient mice reconstituted with PLA2G3-null or DP1-null mast cells, or mast cells cultured with L-PGDS–ablated fibroblasts exhibited impaired maturation and anaphylaxis of mast cells. Thus, we describe a lipid-driven PLA2G3–L-PGDS–DP1 loop that drives mast cell maturation.
Journal of Biological Chemistry | 2016
Remi Murase; Hiroyasu Sato; Kei Yamamoto; Ayako Ushida; Yasumasa Nishito; Kazutaka Ikeda; Tetsuyuki Kobayashi; Toshinori Yamamoto; Yoshitaka Taketomi; Makoto Murakami
Within the secreted phospholipase A2 (sPLA2) family, group X sPLA2 (sPLA2-X) has the highest capacity to hydrolyze cellular membranes and has long been thought to promote inflammation by releasing arachidonic acid, a precursor of pro-inflammatory eicosanoids. Unexpectedly, we found that transgenic mice globally overexpressing human sPLA2-X (PLA2G10-Tg) displayed striking immunosuppressive and lean phenotypes with lymphopenia and increased M2-like macrophages, accompanied by marked elevation of free ω3 polyunsaturated fatty acids (PUFAs) and their metabolites. Studies using Pla2g10-deficient mice revealed that endogenous sPLA2-X, which is highly expressed in the colon epithelium and spermatozoa, mobilized ω3 PUFAs or their metabolites to protect against dextran sulfate-induced colitis and to promote fertilization, respectively. In colitis, sPLA2-X deficiency increased colorectal expression of Th17 cytokines, and ω3 PUFAs attenuated their production by lamina propria cells partly through the fatty acid receptor GPR120. In comparison, cytosolic phospholipase A2 (cPLA2α) protects from colitis by mobilizing ω6 arachidonic acid metabolites, including prostaglandin E2. Thus, our results underscore a previously unrecognized role of sPLA2-X as an ω3 PUFA mobilizer in vivo, segregated mobilization of ω3 and ω6 PUFA metabolites by sPLA2-X and cPLA2α, respectively, in protection against colitis, and the novel role of a particular sPLA2-X-driven PUFA in fertilization.
Journal of Biological Chemistry | 2011
Kei Yamamoto; Yoshitaka Taketomi; Yuki Isogai; Yoshimi Miki; Hiroyasu Sato; Seiko Masuda; Yasumasa Nishito; Kiyokazu Morioka; Yoshikazu Ishimoto; Noriko Suzuki; Yasunori Yokota; Kohji Hanasaki; Yukio Ishikawa; Toshiharu Ishii; Tetsuyuki Kobayashi; Kiyoko Fukami; Kazutaka Ikeda; Hiroki Nakanishi; Ryo Taguchi; Makoto Murakami
Although perturbed lipid metabolism can often lead to skin abnormality, the role of phospholipase A2 (PLA2) in skin homeostasis is poorly understood. In the present study we found that group X-secreted PLA2 (sPLA2-X) was expressed in the outermost epithelium of hair follicles in synchrony with the anagen phase of hair cycling. Transgenic mice overexpressing sPLA2-X (PLA2G10-Tg) displayed alopecia, which was accompanied by hair follicle distortion with reduced expression of genes related to hair development, during a postnatal hair cycle. Additionally, the epidermis and sebaceous glands of PLA2G10-Tg skin were hyperplasic. Proteolytic activation of sPLA2-X in PLA2G10-Tg skin was accompanied by preferential hydrolysis of phosphatidylethanolamine species with polyunsaturated fatty acids as well as elevated production of some if not all eicosanoids. Importantly, the skin of Pla2g10-deficient mice had abnormal hair follicles with noticeable reduction in a subset of hair genes, a hypoplasic outer root sheath, a reduced number of melanin granules, and unexpected up-regulation of prostanoid synthesis. Collectively, our study highlights the spatiotemporal expression of sPLA2-X in hair follicles, the presence of skin-specific machinery leading to sPLA2-X activation, a functional link of sPLA2-X with hair follicle homeostasis, and compartmentalization of the prostanoid pathway in hair follicles and epidermis.
Nature Communications | 2017
Tetsuya Hirabayashi; Tatsuki Anjo; Arisa Kaneko; Yuuya Senoo; Akitaka Shibata; Hiroyuki Takama; Kohei Yokoyama; Yasumasa Nishito; Tomio Ono; Choji Taya; Kazuaki Muramatsu; Kiyoko Fukami; Agustí Muñoz-Garcia; Alan R. Brash; Kazutaka Ikeda; Makoto Arita; Masashi Akiyama; Makoto Murakami
Mutations in patatin-like phospholipase domain-containing 1 (PNPLA1) cause autosomal recessive congenital ichthyosis, but the mechanism involved remains unclear. Here we show that PNPLA1, an enzyme expressed in differentiated keratinocytes, plays a crucial role in the biosynthesis of ω-O-acylceramide, a lipid component essential for skin barrier. Global or keratinocyte-specific Pnpla1-deficient neonates die due to epidermal permeability barrier defects with severe transepidermal water loss, decreased intercellular lipid lamellae in the stratum corneum, and aberrant keratinocyte differentiation. In Pnpla1−/− epidermis, unique linoleate-containing lipids including acylceramides, acylglucosylceramides and (O-acyl)-ω-hydroxy fatty acids are almost absent with reciprocal increases in their putative precursors, indicating that PNPLA1 catalyses the ω-O-esterification with linoleic acid to form acylceramides. Moreover, acylceramide supplementation partially rescues the altered differentiation of Pnpla1−/− keratinocytes. Our findings provide valuable insight into the skin barrier formation and ichthyosis development, and may contribute to novel therapeutic strategies for treatment of epidermal barrier defects.
Journal of Biological Chemistry | 2016
Kei Yamamoto; Yoshimi Miki; Hiroyasu Sato; Yasumasa Nishito; Michael H. Gelb; Yoshitaka Taketomi; Makoto Murakami
Recent studies using knock-out mice for various secreted phospholipase A2 (sPLA2) isoforms have revealed their non-redundant roles in diverse biological events. In the skin, group IIF sPLA2 (sPLA2-IIF), an “epidermal sPLA2” expressed in the suprabasal keratinocytes, plays a fundamental role in epidermal-hyperplasic diseases such as psoriasis and skin cancer. In this study, we found that group IIE sPLA2 (sPLA2-IIE) was expressed abundantly in hair follicles and to a lesser extent in basal epidermal keratinocytes in mouse skin. Mice lacking sPLA2-IIE exhibited skin abnormalities distinct from those in mice lacking sPLA2-IIF, with perturbation of hair follicle ultrastructure, modest changes in the steady-state expression of a subset of skin genes, and no changes in the features of psoriasis or contact dermatitis. Lipidomics analysis revealed that sPLA2-IIE and -IIF were coupled with distinct lipid pathways in the skin. Overall, two skin sPLA2s, hair follicular sPLA2-IIE and epidermal sPLA2-IIF, play non-redundant roles in distinct compartments of mouse skin, underscoring the functional diversity of multiple sPLA2s in the coordinated regulation of skin homeostasis and diseases.
Nature Medicine | 2017
Yuta Shimanaka; Nozomu Kono; Yoshitaka Taketomi; Makoto Arita; Yoshimichi Okayama; Yuki Tanaka; Yasumasa Nishito; Tatsuki Mochizuki; Hiroyuki Kusuhara; Alexander Adibekian; Benjamin F. Cravatt; Makoto Murakami; Hiroyuki Arai
Critical to the function of mast cells in immune responses including allergy is their production of lipid mediators, among which only omega-6 (ω-6) arachidonate–derived eicosanoids have been well characterized. Here, by employing comprehensive lipidomics, we identify omega-3 (ω-3) fatty acid epoxides as new mast cell–derived lipid mediators and show that they are produced by PAF-AH2, an oxidized-phospholipid-selective phospholipase A2. Genetic or pharmacological deletion of PAF-AH2 reduced the steady-state production of ω-3 epoxides, leading to attenuated mast cell activation and anaphylaxis following FcɛRI cross-linking. Mechanistically, the ω-3 epoxides promote IgE-mediated activation of mast cells by downregulating Srcin1, a Src-inhibitory protein that counteracts FcɛRI signaling, through a pathway involving PPARg. Thus, the PAF-AH2–ω-3 epoxide–Srcin1 axis presents new potential drug targets for allergic diseases.
Scientific Reports | 2017
Remi Murase; Yoshitaka Taketomi; Yoshimi Miki; Yasumasa Nishito; Moe Saito; Kiyoko Fukami; Kei Yamamoto; Makoto Murakami
Lipid mediators play pivotal roles in colorectal cancer and colitis, but only a limited member of the phospholipase A2 (PLA2) subtypes, which lie upstream of various lipid mediators, have been implicated in the positive or negative regulation of these diseases. Clinical and biochemical evidence suggests that secreted PLA2 group III (sPLA2-III) is associated with colorectal cancer, although its precise role remains obscure. Here we have found that sPLA2-III-null (Pla2g3−/−) mice are highly resistant to colon carcinogenesis. Furthermore, Pla2g3−/− mice are less susceptible to dextran sulfate-induced colitis, implying that the amelioration of colonic inflammation by sPLA2-III ablation may underlie the protective effect against colon cancer. Lipidomics analysis of the colon revealed significant reduction of pro-inflammatory/pro-tumorigenic lysophosholipids as well as unusual steady-state elevation of colon-protective fatty acids and their oxygenated metabolites in Pla2g3−/− mice. Overall, our results establish a role of sPLA2-III in the promotion of colorectal inflammation and cancer, expand our understanding of the divergent roles of multiple PLA2 enzymes in the gastrointestinal tract, and point to sPLA2-III as a novel druggable target for colorectal diseases.
Cell Metabolism | 2014
Hiroyasu Sato; Yoshitaka Taketomi; Ayako Ushida; Yuki Isogai; Takumi Kojima; Tetsuya Hirabayashi; Yoshimi Miki; Kei Yamamoto; Yasumasa Nishito; Tetsuyuki Kobayashi; Kazutaka Ikeda; Ryo Taguchi; Shuntaro Hara; Satoshi Ida; Yuji Miyamoto; Masayuki Watanabe; Hideo Baba; Keishi Miyata; Yuichi Oike; Michael H. Gelb; Makoto Murakami
The Japanese Biochemical Society/The Molecular Biology Society of Japan | 2017
Shoji Hata; Kei Yamamoto; Yasumasa Nishito; Fujiko Kitamura; Makoto Murakami; Hiroyuki Sorimachi
The Japanese Biochemical Society/The Molecular Biology Society of Japan | 2017
Hiroko Murakami; Toshiyuki Kobayashi; Hirofumi Kashii; Atsushi Sato; Yoko Hagino; Miho Tanaka; Yasumasa Nishito; Yukio Takamatsu; Shigeo Uchino; Kazutaka Ikeda