TY - JOUR
T1 - Autophagy
T2 - A new concept in autoimmunity regulation and a novel therapeutic option
AU - Bonam, Srinivasa Reddy
AU - Wang, Fengjuan
AU - Muller, Sylviane
N1 - Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/11
Y1 - 2018/11
N2 - Nowadays, pharmacologic treatments of autoinflammatory diseases are largely palliative rather than curative. Most of them result in non-specific immunosuppression, which can be associated with broad disruption of natural and induced immunity with significant and sometimes serious unwanted injuries. Among the novel strategies that are under development, tools that modulate the immune system to restore normal tolerance mechanisms are central. In these approaches, peptide therapeutics constitute a class of agents that display many physicochemical advantages. Within this class of potent drugs, the phosphopeptide P140 is very promising for treating patients with lupus, and likely also patients with other chronic inflammatory diseases. We discovered that P140 targets autophagy, a finely orchestrated catabolic process, involved in the regulation of inflammation and in the biology of immune cells. In vitro, P140 acts directly on a particular form of autophagy called chaperone-mediated autophagy, which seems to be hyperactivated in certain subsets of lymphocytes in lupus and in other autoinflammatory settings. In lupus, the “correcting” effect of P140 on autophagy results in a weaker signaling of autoreactive T cells, leading to a significant improvement of pathophysiological status of treated mice. These findings also demonstrated ex vivo in human cells, open novel avenues of therapeutic intervention in pathological conditions, in which specific and not general targeting is highly pursued in the context of the new action plans for personalized medicines.
AB - Nowadays, pharmacologic treatments of autoinflammatory diseases are largely palliative rather than curative. Most of them result in non-specific immunosuppression, which can be associated with broad disruption of natural and induced immunity with significant and sometimes serious unwanted injuries. Among the novel strategies that are under development, tools that modulate the immune system to restore normal tolerance mechanisms are central. In these approaches, peptide therapeutics constitute a class of agents that display many physicochemical advantages. Within this class of potent drugs, the phosphopeptide P140 is very promising for treating patients with lupus, and likely also patients with other chronic inflammatory diseases. We discovered that P140 targets autophagy, a finely orchestrated catabolic process, involved in the regulation of inflammation and in the biology of immune cells. In vitro, P140 acts directly on a particular form of autophagy called chaperone-mediated autophagy, which seems to be hyperactivated in certain subsets of lymphocytes in lupus and in other autoinflammatory settings. In lupus, the “correcting” effect of P140 on autophagy results in a weaker signaling of autoreactive T cells, leading to a significant improvement of pathophysiological status of treated mice. These findings also demonstrated ex vivo in human cells, open novel avenues of therapeutic intervention in pathological conditions, in which specific and not general targeting is highly pursued in the context of the new action plans for personalized medicines.
KW - Autoinflammatory diseases
KW - Autophagy pathways
KW - Modulators of autophagy
KW - Systemic lupus erythematosus
KW - Therapeutic peptides
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U2 - 10.1016/j.jaut.2018.08.009
DO - 10.1016/j.jaut.2018.08.009
M3 - Review article
C2 - 30219390
AN - SCOPUS:85053125515
SN - 0896-8411
VL - 94
SP - 16
EP - 32
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
ER -