Intrinsic factor recognition promotes T helper 17/T helper 1 autoimmune gastric inflammation in patients with pernicious anemia

Arianna Troilo, Alessia Grassi, Luisa Petrone, Fabio Cianchi, Marisa Benagiano, Chiara Della Bella, Nagaja Capitani, Jacopo Bitetti, Sofia D'Elios, Simona Tapinassi, Annalisa Azzurri, Heba Alnwaisri, Jacopo Romagnoli, Nicola Bizzaro, Mathijs Bergman, Cosima Tatiana Baldari, Mario Milco D'Elios*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

The intrinsic factor is the major humoral autoantigen in pernicious anemia/ autoimmune gastritis. Although many studies have examined the autoantibody response to intrinsic factor and H+,K+-ATPase, no information is available on possible pathogenic mechanisms mediated by intrinsic factor - specific gastric T cells. Aim of this study was to investigate intrinsic factor-specific T cells in the gastric mucosa of pernicious anemia patients and define their functional properties. For the first time we provide evidence that gastric mucosa of pernicious anemia patients harbour a high proportion (20%) of autoreactive activated CD4+ T-cell clones that specifically recognize intrinsic factor. Most of these clones (94%) showed a T helper 17 or T helper 1 profile. All intrinsic factor-specific clones produced tumor necrosis factor-a, interleukin-21 and provided substantial help for B-cell immunoglobulin production. Most mucosa-derived intrinsic factor-specific T-cell clones expressed cytotoxicity against target cells. Our results indicate that activation of intrinsic factor-specific T helper 17 and T helper 1 T cells in the gastric mucosa represent a key effector mechanism in pernicious anemia suggesting that the T helper 17/T helper 1 pathway may represent a novel target for the prevention and treatment of the disease.

Original languageEnglish
Pages (from-to)2921-2929
Number of pages9
JournalOncotarget
Volume10
Issue number30
DOIs
Publication statusPublished - 23 Apr 2019

Keywords

  • Atrophic gastritis
  • Interferon-gamma
  • Interleukin-17
  • Intrinsic factor
  • Pernicious anemia

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    Troilo, A., Grassi, A., Petrone, L., Cianchi, F., Benagiano, M., Bella, C. D., ... D'Elios, M. M. (2019). Intrinsic factor recognition promotes T helper 17/T helper 1 autoimmune gastric inflammation in patients with pernicious anemia. Oncotarget, 10(30), 2921-2929. https://doi.org/10.18632/oncotarget.26874