RRC ID 21270
Author Kayes T, Fang Y, Yu S, Downey E, Wang S, Braley-Mullen H.
Title Agonistic anti-CD40 induces thyrocyte proliferation and promotes thyroid autoimmunity by increasing CD40 expression on thyroid epithelial cells.
Journal 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.
Volume 190(8)
Pages 3928-38
Published 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 4.539
Times Cited 5
Mice NOD.Cg-Fcer1g<tm1Rav> Fcgr2b<tm1Ttk>(RBRC02330)