Increased expression of membrane-bound TGF-β1, GITR, and GITR ligand in patients with autoimmune thyroid disease

Hayashi, Fumiaki; Inoue, Naoya; Iwatani, Yoshinori; Yamashita, Yuka; Yamada, Hiroya; Miyauchi, Akira; Watanabe, Mikio

doi:https://doi.org/10.1016/j.imlet.2025.107036

Increased expression of membrane-bound TGF-β1, GITR, and GITR ligand in patients with autoimmune thyroid disease

Hayashi, Fumiaki; Inoue, Naoya; Iwatani, Yoshinori et al.

Immunology Letters, 2025, 276, 107036

Number of Access:121（2025-10-31 07:05 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/102137

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Title	Increased expression of membrane-bound TGF-β1, GITR, and GITR ligand in patients with autoimmune thyroid disease
Creator	CreatorName Hayashi, Fumiaki
	NRID 1000080710269 1000080710269 researchmap permalink nao1 nao1 CreatorName Inoue, Naoya
	NRID 1000060168581 1000060168581 CreatorName Iwatani, Yoshinori
	CreatorName Yamashita, Yuka
	CreatorName Yamada, Hiroya
	CreatorName Miyauchi, Akira
	NRID 1000050294088 1000050294088 ORCID 0000-0001-5971-9296 0000-0001-5971-9296 researchmap permalink watanabemikio watanabemikio Scopus Author ID 55793188612 55793188612 CreatorName Watanabe, Mikio
Subject	Graves’ disease
	Hashimoto's disease
	Regulatory T cell
	TGF-β1
	GITR
Description	Hayashi F., Inoue N., Iwatani Y., et al. Increased expression of membrane-bound TGF-β1, GITR, and GITR ligand in patients with autoimmune thyroid disease. Immunology Letters 276, 107036 (2025); https://doi.org/10.1016/j.imlet.2025.107036.
Abstract	Regulatory T (Treg) cells, which play an important role in maintaining self-tolerance, are present in the thyroid-infiltrating lymphocytes of patients with autoimmune thyroid disease (AITD). We examined the expression of membrane-bound transforming growth factor-β1 (mTGF-β1), which mediates regulatory function and glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR). The protein in turn may inhibit regulatory function on Treg cells and TGF-β1 receptor II (TGF-βRII) and GITR expression. We also evaluated GITR ligand (GITRL) localization in thyroid tissues. mTGF-β1+ cells proportion in Treg cells was higher in the thyroid of patients with AITD than in their peripheral blood. GITR+ cells proportion among Tregs and Teff cells was also higher in the thyroid than in peripheral blood. GITRL expression in thyrocytes was higher in AITD patients than in healthy subjects. The interaction and balance of mTGF-β1, GITR, TGF-βRII, and GITRL especially thyrocyte GITRL expression, could be critical in AITD pathogenesis.
Publisher	Elsevier B.V.
Source Title	Immunology Letters
Volume (Issue)	276
Page	107036
Date of Issued	2025-05-27
Language	English
Handle URL	https://hdl.handle.net/11094/102137
PISSN	01652478
eISSN	18790542
Relation.isVersionOf	DOI (Publisher Version) https://doi.org/10.1016/j.imlet.2025.107036
Access Rights	embargoed access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
CopyRight	The full-text file will be made open to the public on 27 May 2026 in accordance with the publisher's policy.
oaire:version	Accepted Manuscript
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Immunology Letters. 2025, 276, p. 107036
DC.title	Increased expression of membrane-bound TGF-β1, GITR, and GITR ligand in patients with autoimmune thyroid disease
DC.creator	Hayashi, Fumiaki
	Inoue, Naoya
	Iwatani, Yoshinori
	Yamashita, Yuka
	Yamada, Hiroya
	Miyauchi, Akira
	Watanabe, Mikio
DC.publisher	Elsevier B.V.
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-05-27
DC.identifier	https://doi.org/10.1016/j.imlet.2025.107036
DC.subject	Graves’ disease
	Hashimoto's disease
	Regulatory T cell
	TGF-β1
	GITR
DC.description	Hayashi F., Inoue N., Iwatani Y., et al. Increased expression of membrane-bound TGF-β1, GITR, and GITR ligand in patients with autoimmune thyroid disease. Immunology Letters 276, 107036 (2025); https://doi.org/10.1016/j.imlet.2025.107036.
DCTERMS.abstract	Regulatory T (Treg) cells, which play an important role in maintaining self-tolerance, are present in the thyroid-infiltrating lymphocytes of patients with autoimmune thyroid disease (AITD). We examined the expression of membrane-bound transforming growth factor-β1 (mTGF-β1), which mediates regulatory function and glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR). The protein in turn may inhibit regulatory function on Treg cells and TGF-β1 receptor II (TGF-βRII) and GITR expression. We also evaluated GITR ligand (GITRL) localization in thyroid tissues. mTGF-β1+ cells proportion in Treg cells was higher in the thyroid of patients with AITD than in their peripheral blood. GITR+ cells proportion among Tregs and Teff cells was also higher in the thyroid than in peripheral blood. GITRL expression in thyrocytes was higher in AITD patients than in healthy subjects. The interaction and balance of mTGF-β1, GITR, TGF-βRII, and GITRL especially thyrocyte GITRL expression, could be critical in AITD pathogenesis.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.rights	The full-text file will be made open to the public on 27 May 2026 in accordance with the publisher's policy.
DC.format	102137
citation_title	Increased expression of membrane-bound TGF-β1, GITR, and GITR ligand in patients with autoimmune thyroid disease
citation_author	Hayashi, Fumiaki
	Inoue, Naoya
	Iwatani, Yoshinori
	Yamashita, Yuka
	Yamada, Hiroya
	Miyauchi, Akira
	Watanabe, Mikio
citation_publisher	Elsevier B.V.
citation_language	English
citation_date	2025-05-27
citation_journal_title	Immunology Letters
citation_volume	276
citation_firstpage	107036
citation_doi	https://doi.org/10.1016/j.imlet.2025.107036
citation_public_url	https://hdl.handle.net/11094/102137

Increased expression of membrane-bound TGF-β1, GITR, and GITR ligand in patients with autoimmune thyroid disease

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