A dual role for interferon-γ in the pathogenesis of Sjogren's syndrome-like autoimmune exocrinopathy in the nonobese diabetic mouse

被引:134
作者
Cha, S
Brayer, J
Gao, J
Brown, V
Killedar, S
Yasunari, U
Peck, AB
机构
[1] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA
[2] Univ Florida, Dept Oral Biol, Gainesville, FL 32610 USA
[3] H Lee Moffitt Canc & Res Inst, Tampa, FL 33612 USA
[4] Tsurumi Univ, Dept Microbiol, Yokohama, Kanagawa, Japan
[5] Univ Florida, Ctr Orphaned Autoimmune Dis, Gainesville, FL USA
关键词
D O I
10.1111/j.0300-9475.2004.01508.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Sjogren's syndrome-like autoimmune exocrinopathy (AEC) in the nonobese diabetic (NOD) mouse progresses from a preimmune phase to an immune phase, resulting in dry mouth and/or dry eyes. In the present study, the impact of the prototypical T-helper type 1 cytokine, interferon-gamma (IFN-gamma), on the onset of AEC was investigated using both the IFN-gamma and the IFN-gamma receptor gene knockout mice, NOD.IFN-gamma(-/-) and NOD.IFN-gammal(-/-), respectively. Neither the NOD.IFN-gamma(-/-) nor the NOD.IFN-gammaR(-/-) mice exhibited increased acinar cell apoptosis and abnormal salivary protein expression, typically observed in parental NOD mice prior to disease. Without these preimmune phase abnormalities, NOD.IFN-gamma(-/-) and NOD.IFN-gammaR(-/-) mice showed no subsequent autoimmune responses against the salivary glands at 20 weeks. Interestingly, real-time polymerase chain reaction and electrophoretic gel mobility shift assays suggested that IFN-gamma and STAT1, as well as the transcriptional activity of STAT1 in NOD glands, were increased at birth. Unlike the neonatal submandibular glands of NOD or NOD-scid mice that show abnormal glandular morphogenesis at birth, the submandibular glands of the newly constructed congenic strain, NOD-scid.IFN-gamma(-/-), were found to be normal. Taken together, IFN-gamma appears to play a critical role not only during the later immune phase of AEC, but also the early preimmune phase, independent of effector functions of immune cells. How exactly IFN-gamma functions during this period remains speculative.
引用
收藏
页码:552 / 565
页数:14
相关论文
共 69 条
[51]  
Robinson CP, 1998, ARTHRITIS RHEUM, V41, P150, DOI 10.1002/1529-0131(199801)41:1<150::AID-ART18>3.3.CO
[52]  
2-K
[53]   Characterization of the changing lymphocyte populations and cytokine expression in the exocrine tissues of autoimmune nod mice [J].
Robinson, CP ;
Cornelius, J ;
Bounous, DE ;
Yamamoto, H ;
Humphreys-Beher, MG ;
Peck, AB .
AUTOIMMUNITY, 1998, 27 (01) :29-44
[54]   Transfer of human serum IgG to nonobese diabetic Igμnull mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sjogren's syndrome [J].
Robinson, CP ;
Brayer, J ;
Yamachika, S ;
Esch, TR ;
Peck, AB ;
Stewart, CA ;
Peen, E ;
Jonsson, R ;
Humphreys-Beher, MG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (13) :7538-7543
[55]  
Robinson CP, 1998, ADV EXP MED BIOL, V438, P493
[56]   Genetically programmed development of salivary gland abnormalities in the NOD (Nonobese diabetic)-scid mouse in the absence of detectable lymphocytic infiltration: A potential trigger for sialoadenitis of NOD mice [J].
Robinson, CP ;
Yamamoto, H ;
Peck, AB ;
HumphreysBeher, MG .
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1996, 79 (01) :50-59
[57]   Elevated levels of cysteine protease activity in saliva and salivary glands of the nonobese diabetic (NOD) mouse model for Sjogren syndrome [J].
Robinson, CP ;
Yamachika, S ;
Alford, CE ;
Cooper, C ;
Pichardo, EL ;
Shah, N ;
Peck, AB ;
HumphreysBeher, MG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (11) :5767-5771
[58]  
Saito I, 1999, J IMMUNOL, V162, P2488
[59]  
TALAL N, 1992, RHEUM DIS CLIN N AM, V18, P507
[60]   RENAL TUBULAR ACIDOSIS GLOMERULONEPHRITIS AND IMMUNOLOGIC FACTORS IN SJORGRENS SYNDROME [J].
TALAL, N ;
ZISMAN, E ;
SCHUR, PH .
ARTHRITIS AND RHEUMATISM, 1968, 11 (06) :774-+