The Role of Immune Checkpoint Receptors in Regulating Immune Reactivity in Lupus
Identifieur interne : 000359 ( Main/Exploration ); précédent : 000358; suivant : 000360The Role of Immune Checkpoint Receptors in Regulating Immune Reactivity in Lupus
Auteurs : Kun-Lin Lu [Taïwan] ; Ming-Ying Wu [Taïwan] ; Chi-Hui Wang [Taïwan] ; Chuang-Wei Wang [Taïwan] ; Shuen-Iu Hung [Taïwan] ; Wen-Hung Chung [Taïwan, République populaire de Chine] ; Chun-Bing Chen [Taïwan, République populaire de Chine]Source :
- Cells [ 2073-4409 ] ; 2019.
Abstract
Immune checkpoint receptors with co-stimulatory and co-inhibitory signals are important modulators for the immune system. However, unrestricted co-stimulation and/or inadequate co-inhibition may cause breakdown of self-tolerance, leading to autoimmunity. Systemic lupus erythematosus (SLE) is a complex multi-organ disease with skewed and dysregulated immune responses interacting with genetics and the environment. The close connections between co-signaling pathways and SLE have gradually been established in past research. Also, the recent success of immune checkpoint blockade in cancer therapy illustrates the importance of the co-inhibitory receptors in cancer immunotherapy. Moreover, immune checkpoint blockade could result in substantial immune-related adverse events that mimic autoimmune diseases, including lupus. Together, immune checkpoint regulators represent viable immunotherapeutic targets for the treatment of both autoimmunity and cancer. Therefore, it appears reasonable to treat SLE by restoring the out-of-order co-signaling axis or by manipulating collateral pathways to control the pathogenic immune responses. Here, we review the current state of knowledge regarding the relationships between SLE and the co-signaling pathways of T cells, B cells, dendritic cells, and neutrophils, and highlight their potential clinical implications. Current clinical trials targeting the specific co-signaling axes involved in SLE help to advance such knowledge, but further in-depth exploration is still warranted.
Url:
DOI: 10.3390/cells8101213
PubMed: 31597242
PubMed Central: 6829486
Affiliations:
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Le document en format XML
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<author><name sortKey="Lu, Kun Lin" sort="Lu, Kun Lin" uniqKey="Lu K" first="Kun-Lin" last="Lu">Kun-Lin Lu</name>
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<author><name sortKey="Wang, Chi Hui" sort="Wang, Chi Hui" uniqKey="Wang C" first="Chi-Hui" last="Wang">Chi-Hui Wang</name>
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<author><name sortKey="Wang, Chuang Wei" sort="Wang, Chuang Wei" uniqKey="Wang C" first="Chuang-Wei" last="Wang">Chuang-Wei Wang</name>
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(K.-L.L.);<email>mini_robots@yahoo.com.tw</email>
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<author><name sortKey="Hung, Shuen Iu" sort="Hung, Shuen Iu" uniqKey="Hung S" first="Shuen-Iu" last="Hung">Shuen-Iu Hung</name>
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(S.-I.H.)</nlm:aff>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af2-cells-08-01213">College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 333, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 333</wicri:regionArea>
<wicri:noRegion>Taoyuan 333</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af3-cells-08-01213">Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei 105, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei 105</wicri:regionArea>
<wicri:noRegion>Taipei 105</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af4-cells-08-01213">Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Linkou 333, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Linkou 333</wicri:regionArea>
<wicri:noRegion>Linkou 333</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chung, Wen Hung" sort="Chung, Wen Hung" uniqKey="Chung W" first="Wen-Hung" last="Chung">Wen-Hung Chung</name>
<affiliation><nlm:aff id="af1-cells-08-01213">Chang Gung Memorial Hospital, Linkou 333, Taiwan;<email>johnlu710999@gmail.com</email>
(K.-L.L.);<email>mini_robots@yahoo.com.tw</email>
(M.-Y.W.); ,<email>kiruamairo@gmail.com</email>
(C.-W.W.);<email>hungshueniu@gmail.com</email>
(S.-I.H.)</nlm:aff>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af2-cells-08-01213">College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 333, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 333</wicri:regionArea>
<wicri:noRegion>Taoyuan 333</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af3-cells-08-01213">Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei 105, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei 105</wicri:regionArea>
<wicri:noRegion>Taipei 105</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af4-cells-08-01213">Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Linkou 333, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Linkou 333</wicri:regionArea>
<wicri:noRegion>Linkou 333</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af5-cells-08-01213">Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung 204, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung 204</wicri:regionArea>
<wicri:noRegion>Keelung 204</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af6-cells-08-01213">Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou 333, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou 333</wicri:regionArea>
<wicri:noRegion>Linkou 333</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af7-cells-08-01213">Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen 361000, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen 361000</wicri:regionArea>
<wicri:noRegion>Xiamen 361000</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af8-cells-08-01213">Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 333, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 333</wicri:regionArea>
<wicri:noRegion>Taoyuan 333</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chen, Chun Bing" sort="Chen, Chun Bing" uniqKey="Chen C" first="Chun-Bing" last="Chen">Chun-Bing Chen</name>
<affiliation><nlm:aff id="af1-cells-08-01213">Chang Gung Memorial Hospital, Linkou 333, Taiwan;<email>johnlu710999@gmail.com</email>
(K.-L.L.);<email>mini_robots@yahoo.com.tw</email>
(M.-Y.W.); ,<email>kiruamairo@gmail.com</email>
(C.-W.W.);<email>hungshueniu@gmail.com</email>
(S.-I.H.)</nlm:aff>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af2-cells-08-01213">College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 333, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 333</wicri:regionArea>
<wicri:noRegion>Taoyuan 333</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af3-cells-08-01213">Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei 105, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei 105</wicri:regionArea>
<wicri:noRegion>Taipei 105</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af4-cells-08-01213">Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Linkou 333, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Linkou 333</wicri:regionArea>
<wicri:noRegion>Linkou 333</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af5-cells-08-01213">Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung 204, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung 204</wicri:regionArea>
<wicri:noRegion>Keelung 204</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af6-cells-08-01213">Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou 333, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou 333</wicri:regionArea>
<wicri:noRegion>Linkou 333</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af7-cells-08-01213">Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen 361000, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen 361000</wicri:regionArea>
<wicri:noRegion>Xiamen 361000</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af8-cells-08-01213">Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 333, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 333</wicri:regionArea>
<wicri:noRegion>Taoyuan 333</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Cells</title>
<idno type="eISSN">2073-4409</idno>
<imprint><date when="2019">2019</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en"><p>Immune checkpoint receptors with co-stimulatory and co-inhibitory signals are important modulators for the immune system. However, unrestricted co-stimulation and/or inadequate co-inhibition may cause breakdown of self-tolerance, leading to autoimmunity. Systemic lupus erythematosus (SLE) is a complex multi-organ disease with skewed and dysregulated immune responses interacting with genetics and the environment. The close connections between co-signaling pathways and SLE have gradually been established in past research. Also, the recent success of immune checkpoint blockade in cancer therapy illustrates the importance of the co-inhibitory receptors in cancer immunotherapy. Moreover, immune checkpoint blockade could result in substantial immune-related adverse events that mimic autoimmune diseases, including lupus. Together, immune checkpoint regulators represent viable immunotherapeutic targets for the treatment of both autoimmunity and cancer. Therefore, it appears reasonable to treat SLE by restoring the out-of-order co-signaling axis or by manipulating collateral pathways to control the pathogenic immune responses. Here, we review the current state of knowledge regarding the relationships between SLE and the co-signaling pathways of T cells, B cells, dendritic cells, and neutrophils, and highlight their potential clinical implications. Current clinical trials targeting the specific co-signaling axes involved in SLE help to advance such knowledge, but further in-depth exploration is still warranted.</p>
</div>
</front>
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<author><name sortKey="Austin, H" uniqKey="Austin H">H. Austin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Steevels, T A M" uniqKey="Steevels T">T.A.M. Steevels</name>
</author>
<author><name sortKey="Lebbink, R J" uniqKey="Lebbink R">R.J. Lebbink</name>
</author>
<author><name sortKey="Westerlaken, G H A" uniqKey="Westerlaken G">G.H.A. Westerlaken</name>
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</author>
<author><name sortKey="Meyaard, L" uniqKey="Meyaard L">L. Meyaard</name>
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</analytic>
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<biblStruct><analytic><author><name sortKey="Van Avondt, K" uniqKey="Van Avondt K">K. Van Avondt</name>
</author>
<author><name sortKey="Fritsch Stork, R" uniqKey="Fritsch Stork R">R. Fritsch-Stork</name>
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<author><name sortKey="Derksen, R H" uniqKey="Derksen R">R.H. Derksen</name>
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<author><name sortKey="Meyaard, L" uniqKey="Meyaard L">L. Meyaard</name>
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<biblStruct><analytic><author><name sortKey="Van Avondt, K" uniqKey="Van Avondt K">K. Van Avondt</name>
</author>
<author><name sortKey="Van Der Linden, M" uniqKey="Van Der Linden M">M. van der Linden</name>
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<author><name sortKey="Meyaard, L" uniqKey="Meyaard L">L. Meyaard</name>
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</analytic>
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</TEI>
<affiliations><list><country><li>République populaire de Chine</li>
<li>Taïwan</li>
</country>
</list>
<tree><country name="Taïwan"><noRegion><name sortKey="Lu, Kun Lin" sort="Lu, Kun Lin" uniqKey="Lu K" first="Kun-Lin" last="Lu">Kun-Lin Lu</name>
</noRegion>
<name sortKey="Chen, Chun Bing" sort="Chen, Chun Bing" uniqKey="Chen C" first="Chun-Bing" last="Chen">Chun-Bing Chen</name>
<name sortKey="Chen, Chun Bing" sort="Chen, Chun Bing" uniqKey="Chen C" first="Chun-Bing" last="Chen">Chun-Bing Chen</name>
<name sortKey="Chen, Chun Bing" sort="Chen, Chun Bing" uniqKey="Chen C" first="Chun-Bing" last="Chen">Chun-Bing Chen</name>
<name sortKey="Chen, Chun Bing" sort="Chen, Chun Bing" uniqKey="Chen C" first="Chun-Bing" last="Chen">Chun-Bing Chen</name>
<name sortKey="Chen, Chun Bing" sort="Chen, Chun Bing" uniqKey="Chen C" first="Chun-Bing" last="Chen">Chun-Bing Chen</name>
<name sortKey="Chen, Chun Bing" sort="Chen, Chun Bing" uniqKey="Chen C" first="Chun-Bing" last="Chen">Chun-Bing Chen</name>
<name sortKey="Chung, Wen Hung" sort="Chung, Wen Hung" uniqKey="Chung W" first="Wen-Hung" last="Chung">Wen-Hung Chung</name>
<name sortKey="Chung, Wen Hung" sort="Chung, Wen Hung" uniqKey="Chung W" first="Wen-Hung" last="Chung">Wen-Hung Chung</name>
<name sortKey="Chung, Wen Hung" sort="Chung, Wen Hung" uniqKey="Chung W" first="Wen-Hung" last="Chung">Wen-Hung Chung</name>
<name sortKey="Chung, Wen Hung" sort="Chung, Wen Hung" uniqKey="Chung W" first="Wen-Hung" last="Chung">Wen-Hung Chung</name>
<name sortKey="Chung, Wen Hung" sort="Chung, Wen Hung" uniqKey="Chung W" first="Wen-Hung" last="Chung">Wen-Hung Chung</name>
<name sortKey="Chung, Wen Hung" sort="Chung, Wen Hung" uniqKey="Chung W" first="Wen-Hung" last="Chung">Wen-Hung Chung</name>
<name sortKey="Hung, Shuen Iu" sort="Hung, Shuen Iu" uniqKey="Hung S" first="Shuen-Iu" last="Hung">Shuen-Iu Hung</name>
<name sortKey="Hung, Shuen Iu" sort="Hung, Shuen Iu" uniqKey="Hung S" first="Shuen-Iu" last="Hung">Shuen-Iu Hung</name>
<name sortKey="Hung, Shuen Iu" sort="Hung, Shuen Iu" uniqKey="Hung S" first="Shuen-Iu" last="Hung">Shuen-Iu Hung</name>
<name sortKey="Wang, Chi Hui" sort="Wang, Chi Hui" uniqKey="Wang C" first="Chi-Hui" last="Wang">Chi-Hui Wang</name>
<name sortKey="Wang, Chi Hui" sort="Wang, Chi Hui" uniqKey="Wang C" first="Chi-Hui" last="Wang">Chi-Hui Wang</name>
<name sortKey="Wang, Chuang Wei" sort="Wang, Chuang Wei" uniqKey="Wang C" first="Chuang-Wei" last="Wang">Chuang-Wei Wang</name>
<name sortKey="Wang, Chuang Wei" sort="Wang, Chuang Wei" uniqKey="Wang C" first="Chuang-Wei" last="Wang">Chuang-Wei Wang</name>
<name sortKey="Wang, Chuang Wei" sort="Wang, Chuang Wei" uniqKey="Wang C" first="Chuang-Wei" last="Wang">Chuang-Wei Wang</name>
<name sortKey="Wu, Ming Ying" sort="Wu, Ming Ying" uniqKey="Wu M" first="Ming-Ying" last="Wu">Ming-Ying Wu</name>
<name sortKey="Wu, Ming Ying" sort="Wu, Ming Ying" uniqKey="Wu M" first="Ming-Ying" last="Wu">Ming-Ying Wu</name>
</country>
<country name="République populaire de Chine"><noRegion><name sortKey="Chung, Wen Hung" sort="Chung, Wen Hung" uniqKey="Chung W" first="Wen-Hung" last="Chung">Wen-Hung Chung</name>
</noRegion>
<name sortKey="Chen, Chun Bing" sort="Chen, Chun Bing" uniqKey="Chen C" first="Chun-Bing" last="Chen">Chun-Bing Chen</name>
</country>
</tree>
</affiliations>
</record>
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