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. 2022 Nov 3:13:864633.
doi: 10.3389/fimmu.2022.864633. eCollection 2022.

Autoimmunity: Are we asking the right question?

Polly Matzinger  1
Affiliations

Autoimmunity: Are we asking the right question?

Polly Matzinger. Front Immunol. .

Abstract

For decades, the main question immunologists have asked about autoimmunity is "what causes a break in self-tolerance?" We have not found good answers to that question, and I believe we are still so ignorant because it's the wrong question. Rather than a break in self-tolerance, I suggest that many autoimmune diseases might be due to defects in normal tissue physiology.

Keywords: T helper cells (Th cells); autoimmunity; autoreactivity; pregnancy; programmed cell death, danger model; tissue resident cells; tissue-based class control.

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Conflict of interest statement

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

    1. Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol (1994) 12:991–1045. doi: 10.1146/annurev.iy.12.040194.005015 - DOI - PubMed
    1. Matzinger P. An innate sense of danger. Semin Immunol (1998) 10(5):399–415. doi: 10.1006/smim.1998.0143 - DOI - PubMed
    1. Herrmann M, Voll RE, Zoller OM, Hagenhofer M, Ponner BB, Kalden JR. Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus. Arthritis Rheum (1998) 41(7):1241–50. doi: 10.1002/1529-0131(199807)41:7<1241::AID-ART15>3.0.CO;2-H - DOI - PubMed
    1. Matzinger P. Friendly and dangerous signals: is the tissue in control? Nat Immunol (2007) 8(1):11–3. doi: 10.1038/ni0107-11 - DOI - PubMed
    1. Matzinger P, Kamala T. Tissue-based class control: The other side of tolerance. Nat Rev Immunol (2011) 11(3):221–30. doi: 10.1038/nri2940 - DOI - PubMed