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2016 ; 44
(5
): 1034-51
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Co-stimulatory and Co-inhibitory Pathways in Autoimmunity
#MMPMID27192568
Zhang Q
; Vignali DA
Immunity
2016[May]; 44
(5
): 1034-51
PMID27192568
show ga
The immune system is guided by a series of checks and balances, a major component
of which is a large array of co-stimulatory and co-inhibitory pathways that
modulate the host response. Although co-stimulation is essential for boosting and
shaping the initial response following signaling through the antigen receptor,
inhibitory pathways are also critical for modulating the immune response.
Excessive co-stimulation and/or insufficient co-inhibition can lead to a
breakdown of self-tolerance and thus to autoimmunity. In this review, we will
focus on the role of co-stimulatory and co-inhibitory pathways in two systemic
(systemic lupus erythematosus and rheumatoid arthritis) and two organ-specific
(multiple sclerosis and type 1 diabetes) emblematic autoimmune diseases. We will
also discuss how mechanistic analysis of these pathways has led to the
identification of potential therapeutic targets and initiation of clinical trials
for autoimmune diseases, as well as outline some of the challenges that lie
ahead.
|*Receptor Cross-Talk
[MESH]
|Animals
[MESH]
|Arthritis, Rheumatoid/*immunology/therapy
[MESH]
|Autoimmunity
[MESH]
|Costimulatory and Inhibitory T-Cell Receptors/*metabolism
[MESH]
|Diabetes Mellitus, Type 1/*immunology/therapy
[MESH]
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