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Possible Pathogenetic Relevance of Interleukin‐1β in “Destructive” Organ‐specific Autoimmune Disease (Hashimoto's Thyroiditis)
Author(s) -
PAOLIERI F.,
SALMASO C.,
BATTIFORA M.,
MONTAGNA P.,
PESCE G.,
BAGNASCO M.,
RICHIUSA P.,
GALLUZZO A.,
GIORDANO C.
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb07642.x
Subject(s) - thyroiditis , thyroid , antigen , graves' disease , cytokine , autoimmunity , immunology , interleukin , medicine , chemistry , endocrinology , immune system
Thyroid follicular cells (TFC) abundantly express a variety of immunologically relevant surface molecules in Hashimoto's thyroiditis (HT), for example, MHC antigens and adhesion molecules such as ICAM‐1. Cytokines produced by infiltrating type 1 helper and cytotoxic T cells are importantly involved in de novo expression or up‐regulation of such molecules. We recently demonstrated that TFC from HT patients almost invariably bear on their surface two additive functional molecules: Fas/Apo1/CD95, an important participant in apoptosis, and B7.1, a member of a family of “co‐stimulatory” molecules that are crucial for efficient antigen presentation. To date, 12 out of 14 surgical HT thyroid specimens that we studied by immunohistochemistry showed B7.1‐positive TFC, and all showed Fas‐positive TFC, different from Graves' disease (GD) or nonautoimmune specimens. We have investigated the role of a number of cytokines (IL‐1β, TNF‐α, IL‐4, IL‐6, IL‐10, IL‐12, TGF‐β1, IFN‐γ) in regulating B7.1 and Fas expression. The experiments were performed by immunofluorescence flow cytometry on TFC purified from nontoxic goiter specimens which were Fas‐ and B7.1‐negative at baseline, and one B7.1/Fas‐positive HT specimen. IFN‐γ (500 U/mL) and TNF‐α (200 ng/mL) were unable to induce de novo expression of B7.1 or Fas on cultured TFC. At higher doses (2000 U/mL and 800 ng/mL, respectively), they were unable to induce B7.1, but potentiated the spontaneous expression of Fas. Type 2 cytokines (IL‐4 and IL‐10) were unable to induce Fas or B7.1 on TFC at all, or to down‐regulate Fas or B7.1 when expressed. On the other hand, IL‐1β was the only cytokine able to induce Fas expression on Fas‐negative TFC at doses ranging from 100 to 1000 pg/mL. Moreover, at a dose of 400 pg/mL, it was also able to induce B7.1. We demonstrated by immunohistochemistry that IL‐1β is abundantly present on HT thyroids, including follicular structures. It is conceivable that IFN‐γ, or other cytokines secreted by infiltrating T‐lymphocytes, are able to promote IL‐1β secretion by TFC. In conclusion, a crucial role of IL‐1β in “destructive” organ‐specific autoimmunity may be suggested both for the perpetuation of the autoimmune reaction (induction of efficient autoantigen presentation by TFC, via co‐stimulatory molecules) and in induction of tissue damage via “suicide” Fas/FasL‐mediated TFC interaction.