IL-4-dependent effector phase in autoimmune exocrinopathy as defined by the NOD.IL-4-gene knockout mouse model of Sjögren's syndrome.
NOD mice manifest many features of autoimmune exocrinopathy (Sjögren's syndrome), a disease generally characterized by a chronic, progressive immunological attack against the exocrine tissues of the salivary and lacrimal glands. Previous studies using the NOD congenic partner strain, NOD.Igmu(null), defined an important role for B lymphocytes in the development of xerostomia, implicating autoantibodies reactive with the acetylcholine muscarinic receptor (M3R) as the possible effector mechanism. In the present study, we have examined the impact of the cytokine, interleukin (IL)-4, on autoimmune exocrinopathy by using the IL-4 gene knockout (KO) NOD mouse strain, NOD.IL-4-/-. Despite manifesting the physiological aberrations and marked leukocytic infiltration of the salivary glands characteristic of autoimmune xerostomia in NOD mice, the NOD.IL-4-/- mice do not develop xerostomia. However, NOD.IL-4-/- mice that received adoptively transferred T lymphocytes derived from NOD.Igmu-/- mice progress to xerostomia, thereby reversing the defect. While progression or lack of progression to xerostomia correlated with the ability of the NOD.IL-4-/- mice to express detectable anti-M3R autoantibodies, the precise mechanism of how IL-4 influences the development of autoimmune xerostomia remains speculative.
Brayer
J B
JB
Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32610, USA.
Cha
S
S
Nagashima
H
H
Yasunari
U
U
Lindberg
A
A
Diggs
S
S
Martinez
J
J
Goa
J
J
Humphreys-Beher
M G
MG
Peck
A B
AB
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D004195:Disease Models, Animal; D005088:Exocrine Glands / Q000166:cytology / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D007765:Lacrimal Apparatus / Q000166:cytology / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D018448:Models, Immunological; D012469:Salivary Glands / Q000166:cytology / Q000276:immunology; D012859:Sjogren's Syndrome / Q000276:immunology*
D015847:Interleukin-4