Serpins, Immunity and Autoimmunity: Old Molecules, New Functions

Serine protease inhibitors (serpins) are evolutionary old, structurally conserved molecules which encompass nearly all branches of life. More than 1,000 serpins were characterized to date which are subdivided into 16 subgroups (A–P) according to their common ancestry; among them, 37 are found in hum...

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Veröffentlicht in:Clinical reviews in allergy & immunology 2013-10, Vol.45 (2), p.267-280
Hauptverfasser: Gatto, Mariele, Iaccarino, Luca, Ghirardello, Anna, Bassi, Nicola, Pontisso, Patrizia, Punzi, Leonardo, Shoenfeld, Yehuda, Doria, Andrea
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container_issue 2
container_start_page 267
container_title Clinical reviews in allergy & immunology
container_volume 45
creator Gatto, Mariele
Iaccarino, Luca
Ghirardello, Anna
Bassi, Nicola
Pontisso, Patrizia
Punzi, Leonardo
Shoenfeld, Yehuda
Doria, Andrea
description Serine protease inhibitors (serpins) are evolutionary old, structurally conserved molecules which encompass nearly all branches of life. More than 1,000 serpins were characterized to date which are subdivided into 16 subgroups (A–P) according to their common ancestry; among them, 37 are found in humans. Serpins were termed after their capability to inhibit serine proteases, but mounting evidence suggests that they may achieve a greater deal of functions, ranging from embryological growth to synaptic plasticity, development of both myeloid and lymphoid immune cells, and modulation of apoptosis. Serpins are mainly extracellular molecules, although some of them (namely, ov-serpins or clade B serpins) mostly act inside the cells, being either ubiquitously or tissue-specifically expressed. Among newly characterized serpin functions, regulation of cellular proliferation through apoptosis modulation and proteasome disturbance seems to play a major role. Accordingly, several serpins were found to be hyperexpressed in tumor cells. Indeed, apoptosis dysregulation is likely to be a cornerstone in both tumorigenesis and autoimmunity, since uncontrolled cellular viability results in tumor proliferation, while inefficient disposal of apoptotic debris may favor the rescue of autoreactive immune cells. Such a process was widely documented in systemic lupus erythematosus (SLE). Interestingly, alterations in the expression of some serpins, e.g., the ov-serpin SERPINB3, are being unraveled in patients affected with SLE and other autoimmune disorders, suggesting that a failure in serpin function might affect immune homeostasis and self-tolerance, thereby contributing to autoimmunity. Here, we provide an overview of serpin origin, function, and dysfunction, focusing on human serpins and ov-serpins, with a hub on SERPINB3.
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subjects Allergology
Amino acids
Animals
Antigens, Neoplasm - genetics
Antigens, Neoplasm - metabolism
Apoptosis
Autoimmunity
Cell Growth Processes
Fetal Development
Gene Expression Regulation - immunology
Homeostasis
Humans
Immunology
Internal Medicine
Lupus Erythematosus, Systemic - immunology
Medicine
Medicine & Public Health
Neoplasms - immunology
Protease inhibitors
Self Tolerance
Serine Proteinase Inhibitors - immunology
Serpins - genetics
Serpins - immunology
Serpins - metabolism
Synaptic Transmission
Systemic lupus erythematosus
Thrombin
title Serpins, Immunity and Autoimmunity: Old Molecules, New Functions
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