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Publication : The ITIM Domain-Containing NK Receptor Ly49Q Impacts Pulmonary Infection by Mediating Neutrophil Functions.

First Author  Margraf A Year  2018
Journal  J Immunol Volume  200
Issue  12 Pages  4085-4093
PubMed ID  29712775 Mgi Jnum  J:263321
Mgi Id  MGI:6164076 Doi  10.4049/jimmunol.1701084
Citation  Margraf A, et al. (2018) The ITIM Domain-Containing NK Receptor Ly49Q Impacts Pulmonary Infection by Mediating Neutrophil Functions. J Immunol 200(12):4085-4093
abstractText  Pulmonary infection is a frequent pathology associated with excessive neutrophil infiltration. Ly49Q, an ITIM domain-bearing receptor expressed on different leukocytes, has been recently reported to impact neutrophil migration and polarization. Utilizing a murine model of Klebsiella pneumoniae-induced pulmonary infection in combination with additional in vivo and in vitro assays, we show that Ly49Q is critically involved in different steps of the leukocyte adhesion cascade. Ly49Q deficiency is associated with a reduced rolling velocity, impaired crawling capacity, and diminished transmigration. We show that overactivation of the neutrophil beta2 integrins Mac-1 and LFA-1 is responsible for increased adhesion and reduced neutrophil transmigration, resulting in a strongly impaired immune defense against pulmonary infection. Structure function analysis in vitro and in vivo demonstrated that different domains of Ly49Q are important for its function. In summary, Ly49Q regulates integrin activation and neutrophil recruitment and is required for an adequate immune response in pulmonary infection.
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