Basophils activated via TLR signaling may contribute to pathophysiology of type 1 autoimmune pancreatitis

通过 TLR 信号激活的嗜碱性粒细胞可能导致 1 型自身免疫性胰腺炎的病理生理

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作者:Masato Yanagawa, Kazushige Uchida, Yugo Ando, Takashi Tomiyama, Takashi Yamaguchi, Tsukasa Ikeura, Toshiro Fukui, Akiyoshi Nishio, Yoshiko Uemura, Takayuki Miyara, Hiroyuki Okamoto, Souhei Satoi, Kazuichi Okazaki

Background

Pathophysiology of type 1 autoimmune pancreatitis (AIP) is still unclear. We previously reported that M2 macrophages might play an important role in type 1 AIP. Recently, it has been reported that basophils regulate differentiation to M2 macrophages. In this study, we investigated basophils from the pancreatic tissue and peripheral blood of individuals with type 1 AIP.

Conclusions

Basophils activated via TLR signaling may play an important role in the pathophysiology of type 1 AIP.

Methods

By using immunohistochemistry, we investigated basophils in pancreatic tissue from 13 patients with type 1 AIP and examined expression of toll-like receptors (TLRs) by these cells. Additionally, we obtained peripheral blood samples from 27 healthy subjects, 40 patients with type 1 AIP, 8 patients with alcoholic chronic pancreatitis, 10 patients with bronchial asthma, and 10 patients with atopic dermatitis, and analyzed activation of basophils by stimulating them with ligands of TLR1-9. We also compared TLR expression in basophils from the tissue and blood samples.

Results

Basophils were detected in pancreatic tissues from 10 of 13 patients with type 1 AIP. Flow cytometric analysis revealed that the ratios of basophils activated by TLR4 stimulation in type 1 AIP (9.875 ± 1.148%) and atopic dermatitis (11.768 ± 1.899%) were significantly higher than those in healthy subjects (5.051 ± 0.730%; P < 0.05). Levels of basophils activated by TLR2 stimulation were higher in seven type 1 AIP cases. Furthermore, stimulation of TLR2 and/or TLR4, which were expressed by basophils in pancreas, activated basophils in peripheral blood. Conclusions: Basophils activated via TLR signaling may play an important role in the pathophysiology of type 1 AIP.

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