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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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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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. 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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. 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immunology</subject><subject>Serpins - metabolism</subject><subject>Synaptic Transmission</subject><subject>Systemic lupus erythematosus</subject><subject>Thrombin</subject><issn>1080-0549</issn><issn>1559-0267</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkk1rFTEUhoMo9kN_gBsZEMSFU_M1ScaVl9LaQrULuw-5yZk2JZNcJxOk_97c3lvbSgXJIuHkOS-857wIvSH4gGAsP2VCMREtJqxVrGMte4Z2Sdf1LaZCPq9vrHCLO97voL2crzGmWLH-JdqhjNGOMbKLvvyAaeVj_ticjmOJfr5pTHTNoszJbwufm_Pgmm8pgC0BKvkdfjXHJdrZp5hfoReDCRleb-99dHF8dHF40p6dfz09XJy1thP93EpQTpglAybBWkWG5dApIZUUhPZ2kD3BjjAHmJJlJx22GGhvhl5yJahjbB992MiupvSzQJ716LOFEEyEVLImnDMmOVfqP9DqXnAhZUXf_YVepzLF6uOWwrKOS9xTlyaA9nFI82TsWlQvWMUE55RU6uAJqh4Ho7cpwuBr_VHD-wcNV2DCfJVTKLdjfQySDWinlPMEg15NfjTTjSZYr4OgN0HQNQh6HQS9ntfbrbOyHMH96bjbfAXoBsj1K17C9MD6P1V_A50DuGk</recordid><startdate>20131001</startdate><enddate>20131001</enddate><creator>Gatto, Mariele</creator><creator>Iaccarino, Luca</creator><creator>Ghirardello, Anna</creator><creator>Bassi, Nicola</creator><creator>Pontisso, Patrizia</creator><creator>Punzi, Leonardo</creator><creator>Shoenfeld, Yehuda</creator><creator>Doria, Andrea</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20131001</creationdate><title>Serpins, Immunity and Autoimmunity: Old Molecules, New Functions</title><author>Gatto, Mariele ; Iaccarino, Luca ; Ghirardello, Anna ; Bassi, Nicola ; Pontisso, Patrizia ; Punzi, Leonardo ; Shoenfeld, Yehuda ; Doria, Andrea</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c569t-7e8d6ab3e37ecc81fbf5867876129cf7910d13de021b57d0c0e29af974862d33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Allergology</topic><topic>Amino acids</topic><topic>Animals</topic><topic>Antigens, Neoplasm - genetics</topic><topic>Antigens, Neoplasm - metabolism</topic><topic>Apoptosis</topic><topic>Autoimmunity</topic><topic>Cell Growth Processes</topic><topic>Fetal Development</topic><topic>Gene Expression Regulation - immunology</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Immunology</topic><topic>Internal Medicine</topic><topic>Lupus Erythematosus, Systemic - immunology</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Neoplasms - immunology</topic><topic>Protease inhibitors</topic><topic>Self Tolerance</topic><topic>Serine Proteinase Inhibitors - immunology</topic><topic>Serpins - genetics</topic><topic>Serpins - immunology</topic><topic>Serpins - metabolism</topic><topic>Synaptic Transmission</topic><topic>Systemic lupus erythematosus</topic><topic>Thrombin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gatto, Mariele</creatorcontrib><creatorcontrib>Iaccarino, Luca</creatorcontrib><creatorcontrib>Ghirardello, Anna</creatorcontrib><creatorcontrib>Bassi, Nicola</creatorcontrib><creatorcontrib>Pontisso, Patrizia</creatorcontrib><creatorcontrib>Punzi, Leonardo</creatorcontrib><creatorcontrib>Shoenfeld, Yehuda</creatorcontrib><creatorcontrib>Doria, Andrea</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>Proquest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical reviews in allergy & immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gatto, Mariele</au><au>Iaccarino, Luca</au><au>Ghirardello, Anna</au><au>Bassi, Nicola</au><au>Pontisso, Patrizia</au><au>Punzi, Leonardo</au><au>Shoenfeld, Yehuda</au><au>Doria, Andrea</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serpins, Immunity and Autoimmunity: Old Molecules, New Functions</atitle><jtitle>Clinical reviews in allergy & immunology</jtitle><stitle>Clinic Rev Allerg Immunol</stitle><addtitle>Clin Rev Allergy Immunol</addtitle><date>2013-10-01</date><risdate>2013</risdate><volume>45</volume><issue>2</issue><spage>267</spage><epage>280</epage><pages>267-280</pages><issn>1080-0549</issn><eissn>1559-0267</eissn><abstract>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.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>23325331</pmid><doi>10.1007/s12016-013-8353-3</doi><tpages>14</tpages></addata></record> |
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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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