| RRC ID |
21270
|
| 著者 |
Kayes T, Fang Y, Yu S, Downey E, Wang S, Braley-Mullen H.
|
| タイトル |
Agonistic anti-CD40 induces thyrocyte proliferation and promotes thyroid autoimmunity by increasing CD40 expression on thyroid epithelial cells.
|
| ジャーナル |
J Immunol
|
| Abstract |
CD40 is expressed on cells of the immune system and in some tissues that are targets for autoimmune-mediated damage. It is not known if CD40 expression in target tissues plays a role in the pathology of autoimmune diseases. This study shows that agonistic anti-CD40 induces strong and sustained proliferation of thyroid epithelial cells (TECs), or thyrocytes, in IFN-γ(-/-) autoimmune-prone NOD and NOD.H-2h4 mice. TEC proliferation is accompanied by greatly increased expression of CD40 on TECs, development of fibrosis and hypothyroidism, and increased expression of proinflammatory molecules in thyroids. Bone marrow chimera experiments indicate that TEC expression of CD40 is required for anti-CD40-induced TEC proliferation, but lymphoid cells do not have to express CD40. TEC proliferation is reduced in wild-type mice given anti-CD40, presumably because they produce IFN-γ, which inhibits TEC proliferation. CD40 also increases on TECs during development of an autoimmune thyroid disease characterized by TEC hyperproliferation that develops spontaneously in IFN-γ(-/-) NOD.H-2h4 mice. TEC hyperproliferation development is accelerated in mice given agonistic anti-CD40. These studies provide new information regarding the role of target tissue expression of CD40 in development of autoimmunity and suggest that use of agonistic anti-CD40 for tumor therapy could result in autoimmune disease.
|
| 巻・号 |
190(8)
|
| ページ |
3928-38
|
| 公開日 |
2013-4-15
|
| DOI |
10.4049/jimmunol.1202929
|
| PII |
jimmunol.1202929
|
| PMID |
23509363
|
| PMC |
PMC3622184
|
| MeSH |
Animals
Antibodies / physiology*
Autoimmunity*
CD40 Antigens / agonists*
CD40 Antigens / biosynthesis
CD40 Antigens / immunology*
Cell Proliferation*
Epithelial Cells / immunology*
Epithelial Cells / metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Inbred DBA
Mice, Inbred NOD
Mice, Knockout
Mice, SCID
Primary Cell Culture
Thyroid Gland / cytology
Thyroid Gland / immunology*
Thyroid Gland / metabolism*
|
| IF |
4.886
|
| 引用数 |
8
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC02330 |
