TY - JOUR
T1 - Bidirectional crosstalk between neutrophils and adipocytes promotes adipose tissue inflammation
AU - Watanabe, Yasuharu
AU - Nagai, Yoshinori
AU - Honda, Hiroe
AU - Okamoto, Naoki
AU - Yanagibashi, Tsutomu
AU - Ogasawara, Masaru
AU - Yamamoto, Seiji
AU - Imamura, Ryu
AU - Takasaki, Ichiro
AU - Hara, Hiromitsu
AU - Sasahara, Masakiyo
AU - Arita, Makoto
AU - Hida, Shigeaki
AU - Taniguchi, Shun'ichiro
AU - Suda, Takashi
AU - Takatsu, Kiyoshi
N1 - Funding Information:
The authors thank all members of the University of Toyama and Toyama Prefectural Institute for Pharmaceutical Research laboratories for helpful discussions. The authors are grateful to Dr. Shizuo Akira (Immunology Frontier Research Center, Osaka University, Osaka, Japan) for providing Tlr4-/-, Myd88-/-, and Ticam1-/- mice. The authors also thank Dr. Kensuke Miyake (The University of Tokyo, Tokyo, Japan) and Dr. Hiroko Tsutsui (Hyogo Medical College, Hyogo, Japan) for providing Rp105-/- mice and Casp1-/- mice, respectively; Dr. Paul W. Kincade (Oklahoma Medical Research Foundation, Oklahoma City, OK, USA) for critical review of the manuscript; and Michelle Kahmeyer-Gabbe (Edanz Group, Fukoka, Japan; www.edanz.com/ac) for editing a draft of this manuscript. The authors sincerely thank Toyama Prefecture for laboratory support. This work was also supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS Kakenhi Grants JP16K19532 to Y.W. and JP15K08527 to Y.N.), and grants from Presto, Japan Science and Technology Agency (JST; to Y.N.), Hokuriku Life Science Cluster, Ministry of Education, Culture, Sports, Science and Technology (MEXT) Regional Innovation Strategy Support Program (to K.T.), Takeda Science Foundation (to Y.W.), First Bank of Toyama Scholarship Foundation (Y.W.), and the Tokyo Biochemical Research Foundation (to Y.W.). Y.N. and K.T. are joint senior authors. The authors declare no conflicts of interest.
Funding Information:
The authors thank all members of the University of Toyama and Toyama Prefectural Institute for Pharmaceutical Research laboratories for helpful discussions. The authors are grateful to Dr. Shizuo Akira (Immunology Frontier Research Center, Osaka University, Osaka, Japan) for providing , , and mice. The authors also thank Dr. Kensuke Miyake (The University of Tokyo, Tokyo, Japan) and Dr. Hiroko Tsutsui (Hyogo Medical College, Hyogo, Japan) for providing mice and mice, respectively; Dr. Paul W. Kincade (Oklahoma Medical Research Foundation, Oklahoma City, OK, USA) for critical review of the manuscript; and Michelle Kahmeyer‐Gabbe (Edanz Group, Fukoka, Japan; www.edanz.com/ac ) for editing a draft of this manuscript. The authors sincerely thank Toyama Prefecture for laboratory support. This work was also supported by a Grant‐in‐Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS Kakenhi Grants JP16K19532 to Y.W. and JP15K08527 to Y.N.), and grants from Presto, Japan Science and Technology Agency (JST; to Y.N.), Hokuriku Life Science Cluster, Ministry of Education, Culture, Sports, Science and Technology (MEXT) Regional Innovation Strategy Support Program (to K.T.), Takeda Science Foundation (to Y.W.), First Bank of Toyama Scholarship Foundation (Y.W.), and the Tokyo Biochemical Research Foundation (to Y.W.). Y.N. and K.T. are joint senior authors. The authors declare no conflicts of interest. Tlr4 ‐/‐ Myd88 ‐/‐ Ticam1 ‐/‐ Rp105 ‐/‐ Casp1 ‐/‐
Publisher Copyright:
© FASEB
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Chronic activation of the IL-1β system in adipose tissue on metabolic disorders is well demonstrated. However, a mechanism for its expression and activation in the tissue has remained unexplored. Here, we demonstrate that IL-1β transcript was enriched in neutrophils of white adipose tissue (WAT) from lean mice. Mechanistically, the interaction of neutrophils with adipocytes induced IL-1β expression via NF-κB pathway. Lipolysis of adipocytes accumulated neutrophils prior to macrophages in WAT and produced high levels of IL-1β via an inflammasome pathway. Leukotriene B4 (LTB4) production in WAT also contributed to neutrophil accumulation. Furthermore, an LTB4-inflammasome axis contributed to the expression of chemotactic molecules involved in high-fat diet-induced macrophage infiltration into WAT. We have identified previously unappreciated roles for neutrophils in the development of adipose tissue inflammation: robust IL-1β production and infiltration of macrophages to initiate chronic inflammation.—Watanabe, Y., Nagai, Y., Honda, H., Okamoto, N., Yanagibashi, T., Ogasawara, M., Yamamoto, S., Imamura, R., Takasaki, I., Hara, H., Sasahara, M., Arita, M., Hida, S., Taniguchi, S., Suda, T., Takatsu, K. Bidirectional crosstalk between neutrophils and adipocytes promotes adipose tissue inflammation. FASEB J. 33, 11821-11835 (2019). www.fasebj.org.
AB - Chronic activation of the IL-1β system in adipose tissue on metabolic disorders is well demonstrated. However, a mechanism for its expression and activation in the tissue has remained unexplored. Here, we demonstrate that IL-1β transcript was enriched in neutrophils of white adipose tissue (WAT) from lean mice. Mechanistically, the interaction of neutrophils with adipocytes induced IL-1β expression via NF-κB pathway. Lipolysis of adipocytes accumulated neutrophils prior to macrophages in WAT and produced high levels of IL-1β via an inflammasome pathway. Leukotriene B4 (LTB4) production in WAT also contributed to neutrophil accumulation. Furthermore, an LTB4-inflammasome axis contributed to the expression of chemotactic molecules involved in high-fat diet-induced macrophage infiltration into WAT. We have identified previously unappreciated roles for neutrophils in the development of adipose tissue inflammation: robust IL-1β production and infiltration of macrophages to initiate chronic inflammation.—Watanabe, Y., Nagai, Y., Honda, H., Okamoto, N., Yanagibashi, T., Ogasawara, M., Yamamoto, S., Imamura, R., Takasaki, I., Hara, H., Sasahara, M., Arita, M., Hida, S., Taniguchi, S., Suda, T., Takatsu, K. Bidirectional crosstalk between neutrophils and adipocytes promotes adipose tissue inflammation. FASEB J. 33, 11821-11835 (2019). www.fasebj.org.
KW - IL-1β inflammasome
KW - fatty acid
KW - metabolic disorder
UR - http://www.scopus.com/inward/record.url?scp=85074380001&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074380001&partnerID=8YFLogxK
U2 - 10.1096/fj.201900477RR
DO - 10.1096/fj.201900477RR
M3 - Article
C2 - 31355683
AN - SCOPUS:85074380001
SN - 0892-6638
VL - 33
SP - 11821
EP - 11835
JO - FASEB Journal
JF - FASEB Journal
IS - 11
ER -