Toll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4-mediated inflammatory monocyte migration

Naoya Totsuka, Yun Gi Kim, Kazumasa Kanemaru, Kouta Niizuma, Eiji Umemoto, Kei Nagai, Satoko Tahara-Hanaoka, Chigusa Nakahasi-Oda, Shin Ichiro Honda, Masayuki Miyasaka, Kazuko Shibuya, Akira Shibuya

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number4710
JournalNature communications
Volume5
DOIs
Publication statusPublished - 2014 Aug 19
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Totsuka, N., Kim, Y. G., Kanemaru, K., Niizuma, K., Umemoto, E., Nagai, K., Tahara-Hanaoka, S., Nakahasi-Oda, C., Honda, S. I., Miyasaka, M., Shibuya, K., & Shibuya, A. (2014). Toll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4-mediated inflammatory monocyte migration. Nature communications, 5, [4710]. https://doi.org/10.1038/ncomms5710