TY - JOUR
T1 - Toll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4-mediated inflammatory monocyte migration
AU - Totsuka, Naoya
AU - Kim, Yun Gi
AU - Kanemaru, Kazumasa
AU - Niizuma, Kouta
AU - Umemoto, Eiji
AU - Nagai, Kei
AU - Tahara-Hanaoka, Satoko
AU - Nakahasi-Oda, Chigusa
AU - Honda, Shin Ichiro
AU - Miyasaka, Masayuki
AU - Shibuya, Kazuko
AU - Shibuya, Akira
N1 - Funding Information:
We thank S. Mitsuishi and Y. Nomura for secretarial assistance, and the members of the laboratory for their discussions. This work was supported in part by grants provided by the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2014/8/19
Y1 - 2014/8/19
N2 - Inflammatory monocytes play an important role in host defense against infections. However, the regulatory mechanisms of transmigration into infected tissue are not yet completely understood. Here we show that mice deficient in MAIR-II (also called CLM-4 or LMIR2) are more susceptible to caecal ligation and puncture (CLP)-induced peritonitis than wild-type (WT) mice. Adoptive transfer of inflammatory monocytes from WT mice, but not from MAIR-II, TLR4 or MyD88-deficient mice, significantly improves survival of MAIR-II-deficient mice after CLP. Migration of inflammatory monocytes into the peritoneal cavity after CLP, which is dependent on VLA-4, is impaired in above mutant and FcRI 3 chain-deficient mice. Lipopolysaccharide stimulation induces association of MAIR-II with FcRI 3 chain and Syk, leading to enhancement of VLA-4-mediated adhesion to VCAM-1. These results indicate that activation of MAIR-II/FcRI 3 chain by TLR4/MyD88-mediated signalling is essential for the transmigration of inflammatory monocytes from the blood to sites of infection mediated by VLA-4.
AB - Inflammatory monocytes play an important role in host defense against infections. However, the regulatory mechanisms of transmigration into infected tissue are not yet completely understood. Here we show that mice deficient in MAIR-II (also called CLM-4 or LMIR2) are more susceptible to caecal ligation and puncture (CLP)-induced peritonitis than wild-type (WT) mice. Adoptive transfer of inflammatory monocytes from WT mice, but not from MAIR-II, TLR4 or MyD88-deficient mice, significantly improves survival of MAIR-II-deficient mice after CLP. Migration of inflammatory monocytes into the peritoneal cavity after CLP, which is dependent on VLA-4, is impaired in above mutant and FcRI 3 chain-deficient mice. Lipopolysaccharide stimulation induces association of MAIR-II with FcRI 3 chain and Syk, leading to enhancement of VLA-4-mediated adhesion to VCAM-1. These results indicate that activation of MAIR-II/FcRI 3 chain by TLR4/MyD88-mediated signalling is essential for the transmigration of inflammatory monocytes from the blood to sites of infection mediated by VLA-4.
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U2 - 10.1038/ncomms5710
DO - 10.1038/ncomms5710
M3 - Article
C2 - 25134989
AN - SCOPUS:84907318928
SN - 2041-1723
VL - 5
JO - Nature Communications
JF - Nature Communications
M1 - 4710
ER -