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

J Gastroenterol. 2018 Mar;53(3):449-460. doi: 10.1007/s00535-017-1390-6. Epub 2017 Sep 18.

Abstract

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.

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.

Keywords: Autoimmune pancreatitis; Basophil; M2 macrophage; TLR.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoimmune Diseases / metabolism*
  • Autoimmune Diseases / physiopathology
  • Basophils / metabolism*
  • Female
  • Hospitals, University
  • Humans
  • Immunoglobulin G / blood
  • Japan
  • Male
  • Middle Aged
  • Pancreatitis / immunology*
  • Pancreatitis / metabolism*
  • Pancreatitis / physiopathology
  • Signal Transduction
  • Toll-Like Receptor 2 / metabolism*
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Immunoglobulin G
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4