PPARβ/δ activation of CD300a controls intestinal immunity

被引：27

作者：

Tanaka, Toshiya ^{[1
]}

Tahara-Hanaoka, Satoko ^{[2
,3
]}

Nabekura, Tsukasa ^{[2
,3
]}

Ikeda, Kaori ^{[1
]}

Jiang, Shuying ^{[4
,5
]}

Tsutsumi, Shuichi ^{[6
]}

Inagaki, Takeshi ^{[7
]}

Magoori, Kenta ^{[7
]}

Higurashi, Takuma ^{[8
]}

Takahashi, Hirokazu ^{[8
]}

Tachibana, Keisuke ^{[9
]}

Tsurutani, Yuya ^{[7
,10
]}

Raza, Sana ^{[1
]}

Anai, Motonobu ^{[1
]}

Minami, Takashi ^{[11
]}

Wada, Youichiro ^{[1
]}

Yokote, Koutaro ^{[10
]}

Doi, Takefumi ^{[9
]}

Hamakubo, Takao ^{[12
]}

Auwerx, Johan ^{[13
]}

Gonzalez, Frank J. ^{[14
]}

Nakajima, Atsushi ^{[8
]}

Aburatani, Hiroyuki ^{[6
]}

Naito, Makoto ^{[4
]}

Shibuya, Akira ^{[2
,3
]}

Kodama, Tatsuhiko ^{[1
]}

Sakai, Juro ^{[7
]}

机构：

[1] Univ Tokyo, RCAST, LSBM, Tokyo 1538904, Japan

[2] Univ Tsukuba, Fac Med, Ctr TARA, Dept Immunol, Tsukuba, Ibaraki 3058575, Japan

[3] Univ Tsukuba, Japan Sci & Technol Agcy, CREST, Tsukuba, Ibaraki 3058575, Japan

[4] Niigata Univ, Grad Sch Med & Dent Sci, Div Cellular & Mol Pathol, Niigata 9518510, Japan

[5] Peruseus Prote, Tokyo 1530041, Japan

[6] Univ Tokyo, RCAST, Genome Sci Div, Tokyo 1538904, Japan

[7] Univ Tokyo, RCAST, Div Metab Med, Tokyo 1538904, Japan

[8] Yokohama City Univ, Sch Med, Div Gastroenterol, Yokohama, Kanagawa 2360004, Japan

[9] Osaka Univ, Grad Sch Pharmaceut Sci, Osaka 5650871, Japan

[10] Chiba Univ, Grad Sch Med, Dept Clin Cell Biol & Med, Chiba 2608670, Japan

[11] Univ Tokyo, RCAST, Lab Vasc Biol, Tokyo 1538904, Japan

[12] Univ Tokyo, RCAST, Dept Quantitat Biol & Med, Tokyo 1538904, Japan

[13] Ecole Polytech Fed Lausanne, Lab Integrat & Syst Physiol, CH-1015 Lausanne, Switzerland

[14] NCI, Ctr Canc Res, Lab Metab, NIH, Bethesda, MD 20892 USA

来源：

SCIENTIFIC REPORTS | 2014年 / 4卷

关键词：

INNATE IMMUNITY; MAST-CELL; DELTA; MACROPHAGES; EXPRESSION; MICE; CHOLESTEROL; LYMPHOCYTES; REGULATORS; MICROBIOTA;

D O I：

10.1038/srep05412

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Macrophages are important for maintaining intestinal immune homeostasis. Here, we show that PPAR beta/delta (peroxisome proliferator-activated receptor beta/delta) 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.

引用

页数：9

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