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Cutting edge: the SLAM family receptor Ly108 controls T cell and neutrophil functions
Duncan Howie1, F Stephen Laroux, Massimo Morra
1Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. duncan.howie@path.ox.ac.uk
Insights
Ly108 regulates both adaptive and innate immunity. Mice lacking Ly108 show reduced IL-4 in CD4(+) T cells and defective neutrophil function, increasing susceptibility to bacterial infection.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Ly108 is a cell surface receptor in the Signaling Lymphocytic Activation Molecule family.
- It is expressed on T cells, B cells, NK cells, and APCs.
- Ly108 is known to influence NK cell cytotoxicity and T cell cytokine production.
Purpose of the Study:
- To investigate the role of Ly108 in immune responses.
- To characterize the immune phenotype of mice with a targeted disruption of Ly108 exons 2 and 3 (Ly108(DeltaE2+3)).
Main Methods:
- In vitro and in vivo assays were used to assess immune cell function.
- Analysis included cytokine production (IL-4, IL-6, IL-12, TNF-alpha) and reactive oxygen species (ROS) production in neutrophils.
- Mice were infected with Leishmania mexicana and Salmonella typhimurium to evaluate susceptibility.
Main Results:
- Ly108(DeltaE2+3) CD4(+) T cells produced significantly less IL-4 compared to wild-type cells.
- Ly108(DeltaE2+3) mice were highly susceptible to Salmonella typhimurium infection.
- Neutrophils from Ly108(DeltaE2+3) mice exhibited defective bactericidal activity due to reduced ROS production, despite increased IL-6, IL-12, and TNF-alpha production.
Conclusions:
- Ly108 plays a critical role in regulating adaptive immune responses, specifically IL-4 production by CD4(+) T cells.
- Ly108 is also a key regulator of innate immunity, controlling neutrophil bactericidal function.
- Ly108 acts as a crucial regulator of both innate and adaptive immunity.
Abstract:
Ly108, a glycoprotein of the signaling lymphocytic activation molecule family of cell surface receptors expressed by T, B, NK, and APCs has been shown to have a role in NK cell cytotoxicity and T cell cytokine responses. In this study, we describe that CD4(+) T cells from mice with a targeted disruption of exons 2 and 3 of Ly108 (Ly108(DeltaE2+3)) produce significantly less IL-4 than wild-type CD4(+) cells, as judged by in vitro assays and by in vivo responses to cutaneous infection with Leishmania mexicana. Surprisingly, neutrophil functions are controlled by Ly108. Ly108(DeltaE2+3) mice are highly susceptible to infection with Salmonella typhimurium, bactericidal activity of Ly108(DeltaE2+3) neutrophils is defective, and their production of IL-6, IL-12, and TNF-alpha is increased. The aberrant bactericidal activity by Ly108(DeltaE2+3) neutrophils is a consequence of severely reduced production of reactive oxygen species following phagocytosis of bacteria. Thus, Ly108 serves as a regulator of both innate and adaptive immune responses.
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