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Possible involvement of Toll-like receptor 7 in the development of type 1 autoimmune pancreatitis

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

High serum immunoglobulin G4 (IgG4) levels and IgG4-positive plasma cell infiltration are characteristic of type 1 autoimmune pancreatitis (AIP). It is unclear whether innate immunity is a cause of type 1 AIP; the possible involvement of microbial infection has been suggested in its pathogenesis. To clarify the pathogenesis of type 1 AIP, we investigated Toll-like receptors (TLRs) in type 1 AIP patients.

Methods

We studied nine cases of type 1 AIP with ten cases of alcoholic chronic pancreatitis (ACP) and three of the samples from non-tumorous lesion of neuroendocrine tumor (NET) as control subjects. We counted the number of TLR1-11-positive cells immunohistochemically stained with anti-TLR1-11 antibodies. To identify TLR-positive cells in pancreata from type 1 AIP patients, we used a double-immunofluorescence method and counted the numbers of identifiable CD68-, CD163-, CD123-, and CD20-positive cells.

Results

In type 1 AIP, TLR7 (8.815 ± 1.755), TLR8 (3.852 ± 1.489), and TLR10 (3.852 ± 0.921) were highly expressed. Only the ratio of TLR7 per monocyte was significantly higher in type 1 AIP (0.053 ± 0.012) than in ACP (0.007 ± 0.004; p < 0.01) and non-tumorous lesion of NET (0.000 ± 0.000; p < 0.01). In type 1 AIP, the CD163 to TLR7 ratio (0.789 ± 0.031) was significantly higher both than that of CD123 to TLR7 ratio (0.034 ± 0.006; p < 0.001) and CD20 to TLR7 ratio (0.029 ± 0.010; p < 0.001).

Conclusions

TLR7 might be key pattern-recognition receptors involved in the development of type 1 AIP.

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Acknowledgments

This study was partially supported by (1) Grant-in-Aid for Scientific Research (C) of the Ministry of Culture and Science of Japan (26461038, 23591017, 24591020), (2) Grant-in-Aid for “Research for Intractable Diseases” Program from the Ministry of Labor and Welfare of Japan, (3) Grants-in-Aid from CREST Japan Science and Technology Agency, and (4) NEXT-Supported Program for Strategic Research Foundation at Private Universities. The authors thank Professor A-Hon Kwon for surgery of pancreas.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan

    Yuri Fukui, Kazushige Uchida, Yutaku Sakaguchi, Toshiro Fukui, Akiyoshi Nishio & Kazuichi Okazaki

  2. Department of Pathology, Kansai Medical University, Hirakata, Japan

    Nobuaki Shikata, Noriko Sakaida & Yoshiko Uemura

  3. Department of Surgery, Kansai Medical University, Hirakata, Japan

    Sohei Satoi

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  1. Yuri Fukui
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Correspondence to Kazuichi Okazaki.

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Fukui, Y., Uchida, K., Sakaguchi, Y. et al. Possible involvement of Toll-like receptor 7 in the development of type 1 autoimmune pancreatitis. J Gastroenterol 50, 435–444 (2015). https://doi.org/10.1007/s00535-014-0977-4

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