130
Views
60
CrossRef citations to date
0
Altmetric
Original Article

Toll-like Receptors and their Role in the Development of Autoimmune Diseases

&
Pages 183-188 | Received 27 Jan 2004, Accepted 25 Mar 2004, Published online: 07 Jul 2009
 

Abstract

Human Toll-like receptors (TLRs) are crucial for the recognition of invading pathogens and for the activation of both innate and adaptive immunity. Upon stimulation, TLRs recruit various protein kinases via several adaptor molecules, such as MyD88, leading to the activation of NFkB. The identification of TLR signaling pathways may unravel molecular mechanisms of self-tolerance and the means underlying the development of autoimmunity.

The maturation of antigen-presenting cells (APCs), in response to signals received by the innate immune system, may lead to the breakdown of tolerance. This process is mainly activated by TLRs that have been triggered by self-antigens.

Auto-reactive B cells are present in the lymphoid tissues of healthy individuals, but since they are subject to self-tolerance mechanisms, they remain silent. However, when tolerance to self-antigens fails, a complex of self-reactive antibodies against self- or cross-reactive DNA co-engages the antigen receptor and the TLRs, leading to a continuous activation of these auto-reactive B cells and the development of autoimmune diseases.

The contribution of TLRs to the production of auto antibodies by such dual-engagement suggests that this signaling pathway may become a target for new therapeutic approaches in autoimmune diseases.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.