alexa Inhibitory ITAMs as novel regulators of immunity.


Journal of Clinical & Cellular Immunology

Author(s): Blank U, Launay P, Benhamou M, Monteiro RC

Abstract Share this page

Abstract Immune homeostasis is regulated by a finely tuned network of positive-negative regulatory mechanisms that guarantees proper surveillance avoiding hyperactivity that would lead to autoimmunity and inflammatory diseases. Immune responses involve the activation of immunoreceptors that contain tyrosine-based activation motifs (ITAMs). One arm of control involves immunoreceptor tyrosine-based inhibitory motif (ITIM)-bearing receptors, which upon co-aggregation initiate an inhibitory signal through recruitment of signal-aborting phosphatases. Recently, a new immunoregulatory function has been ascribed to ITAMs, which represent in fact dual function modules that, under specific configurations termed inhibitory ITAM (ITAMi), can propagate inhibitory signals. One paradigm is the immunoglobulin A (IgA) Fc receptor (FcalphaRI), which, upon interaction with IgA monomers in the absence of antigen, initiates a powerful inhibitory signal involving Src homology 2 domain-containing phosphatase 1 (SHP-1) recruitment that suppresses cell activation launched by a whole variety of heterologous receptors without co-aggregation. This explains the long known function of IgA as an anti-inflammatory isotype. The importance of this control mechanism in immune homeostasis is underlined by the high incidence of autoimmune and allergic diseases in IgA-deficient patients. ITAMi is now described for an increasing number of immunoreceptors with multiple roles in immunity. ITAMi signaling is also exploited by Escherichia coli to achieve immune evasion during sepsis. Here, we review our current understanding of ITAMi regulatory mechanisms in immune responses and discuss its role in immune homeostasis. This article was published in Immunol Rev and referenced in Journal of Clinical & Cellular Immunology

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version