Thymic stromal lymphopoietin promotes lung inflammation through activation of dendritic cells.
Asthma is an epithelial disorder in which T helper 2 (Th2)-type inflammation has a prominent role. Recent studies indicated that a cytokine, thymic stromal lymphopoietin (TSLP), is essential for the development of antigen-induced asthma. The authors used ovalbumin (OVA) sensitization and challenge to induce a murine asthmatic model. The model was confirmed by airway hyperresponsiveness, serum levels of total and OVA-specific immunoglobulin (IgE), histological analysis of lung tissues. The authors found that expression of TSLP was significantly increased in both mRNA and protein levels in mice lungs treated with OVA. The expression of CD40, CD80, and CD86 in bronchoalveolar lavage fluid (BALF) was increased in mice with OVA. Tight correlation between TSLP mRNA and interleukin (IL)-4, IL-5, and IL-13 in BALF was identified. Furthermore, treating mice with TSLP-neutralizing antibody reduced the expression of TSLP mRNA of lungs, CD40, CD80, and CD86 on dendritic cells, and IL-4, IL-5, and IL-13 in the OVA group. This study indicates that TSLP is increased in the airway epithelium in mice treated with OVA. In the lung inflammation model, TSLP activates dendritic cells (DCs) via up-regulation of CD40, CD80, and CD86, then induces the differentiation of prime naive CD4(+) T cells to become proinflammatory Th2 cells. Blocking TSLP is capable of inhibiting the production of Th2 cytokines, thus presents a promising strategy for the treatment of asthma.
Li
Yan-Li
YL
1Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.
Li
Hong-Jia
HJ
Ji
Feng
F
Zhang
Xiao
X
Wang
Rong
R
Hao
Jun-Qing
JQ
Bi
Wen-Xiang
WX
Dong
Liang
L
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D019013:CD40 Antigens / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018793:Interleukin-13 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D020545:Respiratory Mucosa / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
D000906:Antibodies; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D016207:Cytokines; D018793:Interleukin-13; D015848:Interleukin-5; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse