PPARβ 2/δactivation of CD300a controls intestinal immunity

Toshiya Tanaka; Satoko Tahara-Hanaoka; Tsukasa Nabekura; Kaori Ikeda; Shuying Jiang; Shuichi Tsutsumi; Takeshi Inagaki; Kenta Magoori; Takuma Higurashi; Hirokazu Takahashi; Keisuke Tachibana; Yuya Tsurutani; Sana Raza; Motonobu Anai; Takashi Minami; Youichiro Wada; Koutaro Yokote; Takefumi Doi; Takao Hamakubo; Johan Auwerx; Frank J. Gonzalez; Atsushi Nakajima; Hiroyuki Aburatani; Makoto Naito; Akira Shibuya; Tatsuhiko Kodama; Juro Sakai

doi:10.1038/srep05412

PPARβ 2/δactivation of CD300a controls intestinal immunity

Toshiya Tanaka, Satoko Tahara-Hanaoka, Tsukasa Nabekura, Kaori Ikeda, Shuying Jiang, Shuichi Tsutsumi, Takeshi Inagaki, Kenta Magoori, Takuma Higurashi, Hirokazu Takahashi, Keisuke Tachibana, Yuya Tsurutani, Sana Raza, Motonobu Anai, Takashi Minami, Youichiro Wada, Koutaro Yokote, Takefumi Doi, Takao Hamakubo, Johan AuwerxFrank J. Gonzalez, Atsushi Nakajima, Hiroyuki Aburatani, Makoto Naito, Akira Shibuya, Tatsuhiko Kodama, Juro Sakai

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23 Citations (Scopus)

Abstract

Macrophages are important for maintaining intestinal immune homeostasis. Here, we show that PPARβ 2/δ(peroxisome proliferator-activated receptor β2/δ) directly regulates CD300a in macrophages that express the immunoreceptor tyrosine based-inhibitory motif (ITIM)-containing receptor. In mice lacking CD300a, high-fat diet (HFD) causes chronic intestinal inflammation with low numbers of intestinal lymph capillaries and dramatically expanded mesenteric lymph nodes. As a result, these mice exhibit triglyceride malabsorption and reduced body weight gain on HFD. Peritoneal macrophages from Cd300a-/-mice on HFD are classically M1 activated. Activation of toll-like receptor 4 (TLR4)/MyD88 signaling by lipopolysaccharide (LPS) results in prolonged IL-6 secretion in Cd300a-/-macrophages. Bone marrow transplantation confirmed that the phenotype originates from CD300a deficiency in leucocytes. These results identify CD300a-mediated inhibitory signaling in macrophages as a critical regulator of intestinal immune homeostasis.

Original language	English
Article number	5412
Journal	Scientific reports
Volume	4
DOIs	https://doi.org/10.1038/srep05412
Publication status	Published - 2014 Jun 24
Externally published	Yes

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Tanaka, T., Tahara-Hanaoka, S., Nabekura, T., Ikeda, K., Jiang, S., Tsutsumi, S., Inagaki, T., Magoori, K., Higurashi, T., Takahashi, H., Tachibana, K., Tsurutani, Y., Raza, S., Anai, M., Minami, T., Wada, Y., Yokote, K., Doi, T., Hamakubo, T., ... Sakai, J. (2014). PPARβ 2/δactivation of CD300a controls intestinal immunity. Scientific reports, 4, [5412]. https://doi.org/10.1038/srep05412

Tanaka, T, Tahara-Hanaoka, S, Nabekura, T, Ikeda, K, Jiang, S, Tsutsumi, S, Inagaki, T, Magoori, K, Higurashi, T, Takahashi, H, Tachibana, K, Tsurutani, Y, Raza, S, Anai, M, Minami, T, Wada, Y, Yokote, K, Doi, T, Hamakubo, T, Auwerx, J, Gonzalez, FJ, Nakajima, A, Aburatani, H, Naito, M, Shibuya, A, Kodama, T & Sakai, J 2014, 'PPARβ 2/δactivation of CD300a controls intestinal immunity', Scientific reports, vol. 4, 5412. https://doi.org/10.1038/srep05412

@article{44413744b4254717b4713194e8860f79,

title = "PPARβ 2/δactivation of CD300a controls intestinal immunity",

abstract = "Macrophages are important for maintaining intestinal immune homeostasis. Here, we show that PPARβ 2/δ(peroxisome proliferator-activated receptor β2/δ) directly regulates CD300a in macrophages that express the immunoreceptor tyrosine based-inhibitory motif (ITIM)-containing receptor. In mice lacking CD300a, high-fat diet (HFD) causes chronic intestinal inflammation with low numbers of intestinal lymph capillaries and dramatically expanded mesenteric lymph nodes. As a result, these mice exhibit triglyceride malabsorption and reduced body weight gain on HFD. Peritoneal macrophages from Cd300a-/-mice on HFD are classically M1 activated. Activation of toll-like receptor 4 (TLR4)/MyD88 signaling by lipopolysaccharide (LPS) results in prolonged IL-6 secretion in Cd300a-/-macrophages. Bone marrow transplantation confirmed that the phenotype originates from CD300a deficiency in leucocytes. These results identify CD300a-mediated inhibitory signaling in macrophages as a critical regulator of intestinal immune homeostasis.",

author = "Toshiya Tanaka and Satoko Tahara-Hanaoka and Tsukasa Nabekura and Kaori Ikeda and Shuying Jiang and Shuichi Tsutsumi and Takeshi Inagaki and Kenta Magoori and Takuma Higurashi and Hirokazu Takahashi and Keisuke Tachibana and Yuya Tsurutani and Sana Raza and Motonobu Anai and Takashi Minami and Youichiro Wada and Koutaro Yokote and Takefumi Doi and Takao Hamakubo and Johan Auwerx and Gonzalez, {Frank J.} and Atsushi Nakajima and Hiroyuki Aburatani and Makoto Naito and Akira Shibuya and Tatsuhiko Kodama and Juro Sakai",

note = "Funding Information: This work was supported through Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program, Project for Developing Innovation Systems and by the Special Coordination Fund for Science and Technology from the Ministry of Education, Culture, Sports, Science, and Technology. This work was also supported, in part, by Takeda Science Foundation. All animal care was in accordance with the University of Tokyo and Tsukuba University guidelines.",

year = "2014",

month = jun,

day = "24",

doi = "10.1038/srep05412",

language = "English",

volume = "4",

journal = "Scientific Reports",

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T1 - PPARβ 2/δactivation of CD300a controls intestinal immunity

AU - Tanaka, Toshiya

AU - Tahara-Hanaoka, Satoko

AU - Nabekura, Tsukasa

AU - Ikeda, Kaori

AU - Jiang, Shuying

AU - Tsutsumi, Shuichi

AU - Inagaki, Takeshi

AU - Magoori, Kenta

AU - Higurashi, Takuma

AU - Takahashi, Hirokazu

AU - Tachibana, Keisuke

AU - Tsurutani, Yuya

AU - Raza, Sana

AU - Anai, Motonobu

AU - Minami, Takashi

AU - Wada, Youichiro

AU - Yokote, Koutaro

AU - Doi, Takefumi

AU - Hamakubo, Takao

AU - Auwerx, Johan

AU - Gonzalez, Frank J.

AU - Nakajima, Atsushi

AU - Aburatani, Hiroyuki

AU - Naito, Makoto

AU - Shibuya, Akira

AU - Kodama, Tatsuhiko

AU - Sakai, Juro

N1 - Funding Information: This work was supported through Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program, Project for Developing Innovation Systems and by the Special Coordination Fund for Science and Technology from the Ministry of Education, Culture, Sports, Science, and Technology. This work was also supported, in part, by Takeda Science Foundation. All animal care was in accordance with the University of Tokyo and Tsukuba University guidelines.

PY - 2014/6/24

Y1 - 2014/6/24

N2 - Macrophages are important for maintaining intestinal immune homeostasis. Here, we show that PPARβ 2/δ(peroxisome proliferator-activated receptor β2/δ) directly regulates CD300a in macrophages that express the immunoreceptor tyrosine based-inhibitory motif (ITIM)-containing receptor. In mice lacking CD300a, high-fat diet (HFD) causes chronic intestinal inflammation with low numbers of intestinal lymph capillaries and dramatically expanded mesenteric lymph nodes. As a result, these mice exhibit triglyceride malabsorption and reduced body weight gain on HFD. Peritoneal macrophages from Cd300a-/-mice on HFD are classically M1 activated. Activation of toll-like receptor 4 (TLR4)/MyD88 signaling by lipopolysaccharide (LPS) results in prolonged IL-6 secretion in Cd300a-/-macrophages. Bone marrow transplantation confirmed that the phenotype originates from CD300a deficiency in leucocytes. These results identify CD300a-mediated inhibitory signaling in macrophages as a critical regulator of intestinal immune homeostasis.

AB - Macrophages are important for maintaining intestinal immune homeostasis. Here, we show that PPARβ 2/δ(peroxisome proliferator-activated receptor β2/δ) directly regulates CD300a in macrophages that express the immunoreceptor tyrosine based-inhibitory motif (ITIM)-containing receptor. In mice lacking CD300a, high-fat diet (HFD) causes chronic intestinal inflammation with low numbers of intestinal lymph capillaries and dramatically expanded mesenteric lymph nodes. As a result, these mice exhibit triglyceride malabsorption and reduced body weight gain on HFD. Peritoneal macrophages from Cd300a-/-mice on HFD are classically M1 activated. Activation of toll-like receptor 4 (TLR4)/MyD88 signaling by lipopolysaccharide (LPS) results in prolonged IL-6 secretion in Cd300a-/-macrophages. Bone marrow transplantation confirmed that the phenotype originates from CD300a deficiency in leucocytes. These results identify CD300a-mediated inhibitory signaling in macrophages as a critical regulator of intestinal immune homeostasis.

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JF - Scientific Reports

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ER -

PPARβ 2/δactivation of CD300a controls intestinal immunity

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