Role of RANTES in the development of autoimmune tissue injuries in MRL-Fas lpr mice.
MRL-Fas lpr mice spontaneously develop a severe autoimmune disease closely resembling human SLE. To investigate the possible role of RANTES in autoimmune tissue injuries, we have constructed RANTES-deficient MRL-Fas lpr mice by gene targeting. In the RANTES-deficient mice, axillary lymph nodes were significantly reduced in size compared with those of RANTES-intact mice. Flow cytometric analysis revealed that double-negative (DN) T cells were significantly reduced. Image analyzer showed that cell-infiltrated areas in peribronchial lesions were decreased in the lung of RANTES-deficient MRL-Fas lpr mice. Furthermore, we detected continuous expression of RANTES mRNA in the lung of MRL-Fas lpr mice. In contrast, the degree of histological renal injuries and survival rate was similar in both genotypes. We speculate that RANTES is involved in the development of peribronchial pulmonary lesions in MRL-Fas lpr mice. Further studies using RANTES-deficient mice might contribute to the elucidation of the role of RANTES in autoimmune tissue injuries.
Tsukahara
Tsunemichi
T
Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, Chiba, Japan. tsukaha@aol.com
Makino
Yasuhiko
Y
Fujii
Takayuki
T
Ogawa
Makoto
M
Saisho
Hiromitsu
H
Hamano
Yuki
Y
Ueda
Shiro
S
Akikusa
Bunshiro
B
Danoff
Theodore M
TM
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000473:pathology*; D018946:Chemokine CCL5 / Q000502:physiology*; D004247:DNA / Q000276:immunology; D007668:Kidney / Q000473:pathology; D008168:Lung / Q000473:pathology; D008206:Lymphatic Diseases / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout
D001323:Autoantibodies; D018946:Chemokine CCL5; D004247:DNA