Low dose of IL-2 combined with rapamycin restores and maintains the long-term balance of Th17/Treg cells in refractory SLE patients
Identifieur interne : 000992 ( Ncbi/Curation ); précédent : 000991; suivant : 000993Low dose of IL-2 combined with rapamycin restores and maintains the long-term balance of Th17/Treg cells in refractory SLE patients
Auteurs : Chunmiao Zhao [République populaire de Chine] ; Yanfang Chu [République populaire de Chine] ; Zhaoyun Liang [République populaire de Chine] ; Bingying Zhang [République populaire de Chine] ; Xuxia Wang [République populaire de Chine] ; Xiaona Jing [République populaire de Chine] ; Meihua Hao [République populaire de Chine] ; Yiqi Wang [République populaire de Chine] ; Jia An [République populaire de Chine] ; Xingzhe Zhang [République populaire de Chine] ; Liguang Sun [République populaire de Chine] ; Junwei Chen [République populaire de Chine]Source :
- BMC Immunology [ 1471-2172 ] ; 2019.
Abstract
The development of Systemic lupus erythematosus (SLE) has been associated with the balance of Th17 and Treg cells. IL-2 and rapamycin can influence the populations of both Th17 and Treg cells. However, it is unclear whether low dose of IL-2 and rapamycin can relieve the symptoms of SLE patients and what is the mechanisms. In this study, we aim to analyze the effect of low dose of IL-2 plus rapamycin on the number of Tregs, Th17 cells and the ratio of Th17/Treg cells, as well as to evaluate its therapeutic efficacy in refractory SLE patients.
Fifty refractory SLE patients and 70 healthy controls were enrolled and followed up for 24 weeks. We found that compared with HC, the refractory SLE patients had a lower number of Tregs, a similar number of Th17 cells, but an increased ratio of Th17/Treg. After the treatment, the number of Tregs of the patients at 12th and 24th week was significantly increased. While the number of Th17 cells was unchanged, the ratio of Th17/Treg was significantly decreased at both 6 weeks and 24 weeks. After 6, 12 and 24 weeks of treatment, the SLEDAI score was significantly reduced. The prednison dosage at 6th,12th and 24th week post treatment was significantly decreased.
Our results support that the reduction of Tregs and the imbalance of Th17/Treg cells were correlated with the occurrence and development of refractory SLE. Low dose of IL-2 combined with rapamycin was able to restore the number of Tregs and the balance of Th17/Treg cells. As a result, this approach was able to induce immune tolerance and promote disease remission, allowing for the reduction in prednisone dosage.
Url:
DOI: 10.1186/s12865-019-0305-0
PubMed: 31484501
PubMed Central: 6727508
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Chine</country><wicri:regionArea>Taiyuan</wicri:regionArea></affiliation></author><author><name sortKey="Chu, Yanfang" sort="Chu, Yanfang" uniqKey="Chu Y" first="Yanfang" last="Chu">Yanfang Chu</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.452845.a</institution-id><institution>Deptartment of Rheumatology and Immunology,</institution><institution>The Second Hospital of Shanxi Medical University,</institution></institution-wrap>Taiyuan, 030001 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Taiyuan</wicri:regionArea></affiliation></author><author><name sortKey="Liang, Zhaoyun" sort="Liang, Zhaoyun" uniqKey="Liang Z" first="Zhaoyun" last="Liang">Zhaoyun Liang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.452845.a</institution-id><institution>Deptartment of Rheumatology and Immunology,</institution><institution>The Second Hospital of Shanxi Medical University,</institution></institution-wrap>Taiyuan, 030001 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Taiyuan</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Bingying" sort="Zhang, Bingying" uniqKey="Zhang B" first="Bingying" last="Zhang">Bingying Zhang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.452845.a</institution-id><institution>Deptartment of Rheumatology and Immunology,</institution><institution>The Second Hospital of Shanxi Medical University,</institution></institution-wrap>Taiyuan, 030001 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Taiyuan</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Xuxia" sort="Wang, Xuxia" uniqKey="Wang X" first="Xuxia" last="Wang">Xuxia Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.452845.a</institution-id><institution>Deptartment of Rheumatology and Immunology,</institution><institution>The Second Hospital of Shanxi Medical University,</institution></institution-wrap>Taiyuan, 030001 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Taiyuan</wicri:regionArea></affiliation></author><author><name sortKey="Jing, Xiaona" sort="Jing, Xiaona" uniqKey="Jing X" first="Xiaona" last="Jing">Xiaona Jing</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.452845.a</institution-id><institution>Deptartment of Rheumatology and Immunology,</institution><institution>The Second Hospital of Shanxi Medical University,</institution></institution-wrap>Taiyuan, 030001 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Taiyuan</wicri:regionArea></affiliation></author><author><name sortKey="Hao, Meihua" sort="Hao, Meihua" uniqKey="Hao M" first="Meihua" last="Hao">Meihua Hao</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.452845.a</institution-id><institution>Deptartment of Rheumatology and Immunology,</institution><institution>The Second Hospital of Shanxi Medical University,</institution></institution-wrap>Taiyuan, 030001 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Taiyuan</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Yiqi" sort="Wang, Yiqi" uniqKey="Wang Y" first="Yiqi" last="Wang">Yiqi Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.452845.a</institution-id><institution>Deptartment of Rheumatology and Immunology,</institution><institution>The Second Hospital of Shanxi Medical University,</institution></institution-wrap>Taiyuan, 030001 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Taiyuan</wicri:regionArea></affiliation></author><author><name sortKey="An, Jia" sort="An, Jia" uniqKey="An J" first="Jia" last="An">Jia An</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.452845.a</institution-id><institution>Deptartment of Rheumatology and Immunology,</institution><institution>The Second Hospital of Shanxi Medical University,</institution></institution-wrap>Taiyuan, 030001 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Taiyuan</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Xingzhe" sort="Zhang, Xingzhe" uniqKey="Zhang X" first="Xingzhe" last="Zhang">Xingzhe Zhang</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0599 1243</institution-id><institution-id institution-id-type="GRID">grid.43169.39</institution-id><institution>School of Basic Medical Sciences,</institution><institution>Xi’an Jiaotong University,</institution></institution-wrap>Xi’an, 710061 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Xi’an</wicri:regionArea></affiliation></author><author><name sortKey="Sun, Liguang" sort="Sun, Liguang" uniqKey="Sun L" first="Liguang" last="Sun">Liguang Sun</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.430605.4</institution-id><institution>Institute of Translational Medicine,</institution><institution>The First Hospital of Jilin University,</institution></institution-wrap>Changchun, 130021 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Changchun</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Junwei" sort="Chen, Junwei" uniqKey="Chen J" first="Junwei" last="Chen">Junwei Chen</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.452845.a</institution-id><institution>Deptartment of Rheumatology and Immunology,</institution><institution>The Second Hospital of Shanxi Medical University,</institution></institution-wrap>Taiyuan, 030001 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Taiyuan</wicri:regionArea></affiliation></author></analytic><series><title level="j">BMC Immunology</title><idno type="eISSN">1471-2172</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p id="Par1">The development of Systemic lupus erythematosus (SLE) has been associated with the balance of Th17 and Treg cells. IL-2 and rapamycin can influence the populations of both Th17 and Treg cells. However, it is unclear whether low dose of IL-2 and rapamycin can relieve the symptoms of SLE patients and what is the mechanisms. In this study, we aim to analyze the effect of low dose of IL-2 plus rapamycin on the number of Tregs, Th17 cells and the ratio of Th17/Treg cells, as well as to evaluate its therapeutic efficacy in refractory SLE patients.</p></sec><sec><title>Result</title><p id="Par2">Fifty refractory SLE patients and 70 healthy controls were enrolled and followed up for 24 weeks. We found that compared with HC, the refractory SLE patients had a lower number of Tregs, a similar number of Th17 cells, but an increased ratio of Th17/Treg. After the treatment, the number of Tregs of the patients at 12th and 24th week was significantly increased. While the number of Th17 cells was unchanged, the ratio of Th17/Treg was significantly decreased at both 6 weeks and 24 weeks. After 6, 12 and 24 weeks of treatment, the SLEDAI score was significantly reduced. The prednison dosage at 6th,12th and 24th week post treatment was significantly decreased.</p></sec><sec><title>Conclusion</title><p id="Par3">Our results support that the reduction of Tregs and the imbalance of Th17/Treg cells were correlated with the occurrence and development of refractory SLE. Low dose of IL-2 combined with rapamycin was able to restore the number of Tregs and the balance of Th17/Treg cells. As a result, this approach was able to induce immune tolerance and promote disease remission, allowing for the reduction in prednisone dosage.</p></sec><sec><title>Trial registration</title><p id="Par300"><ext-link ext-link-type="uri" xlink:href="http://www.chictr.org.cn/showproj.aspx?proj=15448">ChiCTR-IPR-16009451</ext-link> Registration date: 2016/10/16</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Mak, A" uniqKey="Mak A">A Mak</name></author><author><name sortKey="Kow, Ny" uniqKey="Kow N">NY Kow</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Talaat, Rm" uniqKey="Talaat R">RM Talaat</name></author><author><name sortKey="Mohamed, Sf" uniqKey="Mohamed S">SF Mohamed</name></author><author><name sortKey="Bassyouni, Ih" uniqKey="Bassyouni I">IH Bassyouni</name></author><author><name sortKey="Raouf, Aa" uniqKey="Raouf A">AA 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K">K Ichikawa</name></author><author><name sortKey="Keith, Ct" uniqKey="Keith C">CT Keith</name></author><author><name sortKey="Lane, Ws" uniqKey="Lane W">WS Lane</name></author><author><name sortKey="Schreiber, Sl" uniqKey="Schreiber S">SL Schreiber</name></author></analytic></biblStruct></listBibl></div1></back></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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