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Editorial
. 2022 Sep 30;11(1):2130558.
doi: 10.1080/2162402X.2022.2130558. eCollection 2022.

PDIA3 as a potential bridge between immunogenic cell death and autoreactivity

Jonathan G Pol  1   2 , Céleste Plantureux  3 , María Pérez-Lanzón  1   2 , Guido Kroemer  4
Affiliations
Editorial

PDIA3 as a potential bridge between immunogenic cell death and autoreactivity

Jonathan G Pol et al. Oncoimmunology. .
No abstract available

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Conflict of interest statement

J.G.P. is the inventor of patents covering the diagnosis, prognosis, and treatment of cancers, including patents licensed to Turstone Biologics and Therafast Bio. G.K. declares having held research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Sotio, Tollys, Vascage and Vasculox/Tioma, has received consulting/advisory honoraria from Reithera, is on the Board of Directors of the Bristol Myers Squibb Foundation France, is a scientific co-founder of everImmune, Osasuna Therapeutics, Samsara Therapeutics and Therafast Bio, and is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis and metabolic disorders, including patents licensed to Bayer (WO2014020041-A1, WO2014020043-A1), Bristol-Myers Squibb (WO2008057863-A1), Osasuna Therapeutics (WO2019057742A1), PharmaMar (WO2022048775-A1), Raptor Pharmaceuticals (EP2664326-A1), Samsara Therapeutics (GB202017553D0 and GB202017030D0), and Therafast Bio (EP3684471A1). All other authors declare that they have no potential conflicts of interest. The other authors declare that they have no potential conflicts of interest.

Figures

Figure 1.
Figure 1.
Role of PDIA3 in metabolic disease-related autoreactivity. In step 1, metabolic stress causes cells like hepatocytes to exhibit higher levels of the endoplasmic reticulum chaperone PDIA3 at their surface. This signal may trigger phagocytosis of damaged cells by dendritic cells (DCs). In step 2, these immune sentinels process PDIA3, present related epitopes onto MHC molecules, and then (step 3) prime naïve PDIA3-specific T lymphocytes. In step 4, such T cells differentiate into type-1 (i.e. IFN-γ and TNF-α secreting) and type-17 (i.e. IL-17A secreting) effector or cytotoxic (i.e. GzmB releasing) T lymphocytes, and favor a B cell response culminating in the production of cytopathic anti-PDIA3 IgG antibodies. The resulting autoreactivity increases the risk of developing the indicated chronic inflammatory diseases (step 5). Created with BioRender.com. GzmB, granzyme B; IFN-γ, interferon-γ; IL17, interleukin-17; MHC, major histocompatibility complex; TCR, T cell receptor; TNFα, tumor necrosis factor-α.
See this image and copyright information in PMC

Comment on

  • PDIA3 epitope-driven immune autoreactivity contributes to hepatic damage in type 2 diabetes.
    Clement CC, Osan J, Buque A, Nanaware PP, Chang YC, Perino G, Shetty M, Yamazaki T, Tsai WL, Urbanska AM, Calvo-Calle JM, Ramsamooj S, Ramsamooj S, Vergani D, Mieli-Vergani G, Terziroli Beretta-Piccoli B, Gadina M, Montagna C, Goncalves MD, Sallusto F, Galluzzi L, Soni RK, Stern LJ, Santambrogio L. Clement CC, et al. Sci Immunol. 2022 Aug 12;7(74):eabl3795. doi: 10.1126/sciimmunol.abl3795. Epub 2022 Aug 19. Sci Immunol. 2022. PMID: 35984892 Free PMC article.

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