Enhanced expression of programmed death-1 (PD-1)/PD-L1 in salivary glands of patients with Sjögren's syndrome.
Enhanced expression of programmed death-1 (PD-1)/PD-L1 in salivary glands of patients with Sjögren's syndrome.
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发表时间：
2005-11
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通讯作者：
M. Kobayashi;S. Kawano;S. Hatachi;Chiyo Kurimoto;Taku Okazaki;Yoshiko Iwai;T. Honjo;Yoshimasa Tanaka;N. Minato;T. Komori;S. Maeda;S. Kumagai
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作者：
M. Kobayashi;S. Kawano;S. Hatachi;Chiyo Kurimoto;Taku Okazaki;Yoshiko Iwai;T. Honjo;Yoshimasa Tanaka;N. Minato;T. Komori;S. Maeda;S. Kumagai
目的程序性死亡-1（PD-1）介导负性信号，介导淋巴细胞耐受。PD-1通路的功能障碍被认为会导致自身免疫性疾病，如类风湿性关节炎（RA）。为了研究PD-1/PD-L系统在干燥综合征（SS）病理学中的作用，我们检测了PD-1及其配体PD-L1在SS患者唾液淋巴细胞和唾液腺中的表达。方法采用流式细胞术检测SS唾液淋巴细胞PD-1的表达。用PMA和离子霉素刺激后进行细胞内白细胞介素10（IL-10）染色。采用间接免疫组化法检测PD-1和PD-L1的表达。结果SS患者唾液淋巴细胞PD-1表达的平均荧光强度明显高于正常对照组、RA患者和SLE患者。PD-1阳性SS唾液淋巴细胞在PMA/离子霉素刺激后细胞内表达IL-10。免疫组化分析显示，52%的SS患者唾液腺浸润淋巴细胞上表达PD-1，68%的SS患者导管和腺泡上皮细胞上表达PD-L1。使用HSG细胞的体外分析显示，PD-L1是由干扰素-γ诱导的，而不是由肿瘤坏死因子-α和IL-1 β诱导的。结论SS患者T淋巴细胞表达PD-1，唾液腺上皮细胞表达PD-L1，提示PD-1/PD-L1通路功能障碍可能与淋巴细胞耐受有关，从而导致SS的发生。
OBJECTIVE Programmed death-1 (PD-1) mediates a negative signal and introduces tolerance for lymphocytes. Dysfunction of the PD-1 pathway is thought to result in autoimmune diseases such as rheumatoid arthritis (RA). To investigate the role of the PD-1/PD-L system in the pathology of Sjögren's syndrome (SS), we examined the expression of PD-1 and its ligand PD-L1 in salivary lymphocytes and salivary glands from patients with SS. METHODS Flow cytometry analysis was used to determine expression of PD-1 in SS salivary lymphocytes. Intracellular staining of interleukin 10 (IL-10) was performed after stimulation with PMA and ionomycin. Indirect immunohistochemistry was used to investigate the expression of PD-1 and PD-L1. RESULTS The mean fluorescence intensity of PD-1 expression in SS salivary lymphocytes was significantly higher than that from healthy controls and patients with RA or systemic lupus erythematosus. PD-1-positive SS salivary lymphocytes expressed IL-10 intracellularly upon PMA/ionomycin stimulation. Immunohistochemical analysis showed that PD-1 was expressed on infiltrating lymphocytes in salivary gland from 52% of SS patients, and PD-L1 was expressed on ductal and acinar epithelial cells from 68% of SS patients. In vitro analysis using HSG cells revealed that PD-L1 was induced by interferon-gamma but not by tumor necrosis factor-alpha and IL-1beta. CONCLUSION PD-1 is expressed on T lymphocytes and PD-L1 on epithelial cells from inflamed salivary glands of patients with SS, which suggests that dysfunction of the PD-1/PD-L1 pathway may be related to tolerance for lymphocytes, which causes SS.