Sustained interleukin-6 signalling leads to the development of lymphoid organ-like structures in the lung.
A variety of pathological changes are seen in lymphoproliferative disorders of the lung but the histogenesis of these abnormalities is not yet fully understood. We previously showed that adenovirus vector-mediated transient expression of both the human interleukin-6 (IL-6) and IL-6 receptor (IL-6R) genes, but not the IL-6 gene alone, in the rat lung induced lymphocytic alveolitis. In the present study, we explored the lung pathology of human IL-6 and IL-6R double transgenic mice to elucidate the effects of prolonged IL-6 signalling on the lung. The transgenic animals developed mononuclear cell accumulation in peribronchovascular regions, but little infiltration into alveolar spaces. Immunohistochemical analysis revealed that the cellular accumulations contained not only mixtures of inflammatory cells but also lymphoid tissue-like structures. As the expression of CXCL13/BLC, the indispensable chemokine for lymphoid organogenesis, was recognized in the B cell follicles of the pulmonary lesions, we speculate that this chemokine plays an inductive role in the development of the lymphoid tissue-like structures. These structures were distinguished from bronchus-associated lymphoid tissues (BALTs) by their location and by the lack of lymphoepithelium, which is a characteristic of BALT. These findings imply that IL-6 signalling may play a role in the pathogenesis of lymphoproliferative disorders of the lung.
Goya
Sho
S
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. goyas@med3.med.osaka-u.ac.jp
Matsuoka
Hiroto
H
Mori
Masahide
M
Morishita
Hiroshi
H
Kida
Hiroshi
H
Kobashi
Yoichiro
Y
Kato
Terufumi
T
Taguchi
Yoshio
Y
Osaki
Tadashi
T
Tachibana
Isao
I
Nishimoto
Norihiro
N
Yoshizaki
Kazuyuki
K
Kawase
Ichiro
I
Hayashi
Seiji
S
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001980:Bronchi / Q000276:immunology / Q000473:pathology; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000032:analysis; D007150:Immunohistochemistry / Q000379:methods; D015850:Interleukin-6 / Q000276:immunology*; D008168:Lung / Q000473:pathology*; D008171:Lung Diseases / Q000276:immunology / Q000473:pathology*; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011650:Pulmonary Alveoli / Q000276:immunology / Q000473:pathology; D019947:Receptors, Interleukin-6 / Q000276:immunology
D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D015850:Interleukin-6; D019947:Receptors, Interleukin-6