Tohoku J. Exp. Med., 2023 February, 259(4)

LILRB4/gp49B Co-Localizes with Integrin via Fibronectin at Focal Adhesion Sites on Mast Cells

Shotaro Miyamoto,¹ Takumi Chiba,¹ So Itoi,¹ Mei-Tzu Su¹ and Toshiyuki Takai¹

¹Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan

Mast cells protect a host from invasion by infectious agents and environmental allergens through activation of innate and adaptive immune receptors, their excessive activation being tightly regulated by inhibitory receptors, such as leukocyte immunoglobulin-like receptor (LILR)B4 (gp49B in mice). However, the regulatory mechanism of LILRB4/gp49B expressed on mast cells remains to be clarified in relation to their recently identified ligand, fibronectin (FN), a direct activator of integrins and an indirect stimulator of high-affinity Fc receptor for IgE (FcεRI). Confocal microscopic analysis suggested that gp49B is spatially close to integrin β₁ on non-adhered bone marrow-derived mast cells (BMMCs). Their spatial relatedness increases further at robust focal adhesion sites on cells adhering to immobilized FN. However, the confocal fluorescence signal of the α subunit of FcεRI was found to be correlated to neither gp49B nor integrin β₁ on non-adherent and adherent BMMCs. Stimulation of FcεRI with an immobilized antigen caused FcεRIα signals to accumulate in an inside area surrounded by robust focal adhesion with a concomitant slight increase in the signal correlation of FcεRIα and integrin β₁, accompanied by a less significant increase of the FcεRIα and gp49 correlation. Thus, activating and inhibitory FN receptors integrin and gp49B, respectively, were co-localized via FN at robust focal adhesion sites on BMMCs, while FcεRI was not close to gp49B spatially.

Keywords —— allergy; FcεRI; fibronectin; immune checkpoint; lipid raft

© 2023 Tohoku University Medical Press

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Tohoku J. Exp. Med 2023, 259, 273-284.

Correspondence: Toshiyuki Takai, Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.

e-mail: toshiyuki.takai.b8@tohoku.ac.jp