Cutting edge: the SLAM family receptor Ly108 controls T cell and neutrophil functions.
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.
Howie
Duncan
D
Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. duncan.howie@path.ox.ac.uk
Laroux
F Stephen
FS
Morra
Massimo
M
Satoskar
Abhay R
AR
Rosas
Lucia E
LE
Faubion
William A
WA
Julien
Aimee
A
Rietdijk
Svend
S
Coyle
Anthony J
AJ
Fraser
Christopher
C
Terhorst
Cox
C
D000818:Animals; D015703:Antigens, CD; D000950:Antigens, Ly / Q000235:genetics / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003433:Crosses, Genetic; D018390:Gene Targeting; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007136:Immunoglobulins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000502:physiology*; D016897:Respiratory Burst / Q000235:genetics / Q000276:immunology; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
D015703:Antigens, CD; D000950:Antigens, Ly; D006023:Glycoproteins; D007136:Immunoglobulins; D015847:Interleukin-4; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; C000604063:Slamf6 protein, mouse