Regulation of the alternative pathway of complement modulates injury and immunity in a chronic model of dextran sulphate sodium-induced colitis
被引:28
作者:
Elvington, M.
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Med Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, Charleston, SC 29425 USAMed Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, Charleston, SC 29425 USA
Elvington, M.
[1
]
Schepp-Berglind, J.
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Med Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, Charleston, SC 29425 USAMed Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, Charleston, SC 29425 USA
Schepp-Berglind, J.
[1
]
Tomlinson, S.
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Med Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, Charleston, SC 29425 USA
Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USAMed Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, Charleston, SC 29425 USA
Tomlinson, S.
[1
,2
]
机构:
[1] Med Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, Charleston, SC 29425 USA
[2] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA
The role of complement in inflammatory bowel disease (IBD) has been studied primarily using acute models, and it is unclear how complement affects processes in more relevant chronic models of IBD in which modulation of adaptive immunity and development of fibrosis have pathogenic roles. Using mice deficient in C1q/mannose-binding lectin (MBL) or C3, we demonstrated an important role for these opsonins and/or the classical pathway C3 convertase in providing protection against mucosal injury and infection in a model of chronic dextran sulphate sodium (DSS)-induced colitis. In contrast, deficiency of the alternative pathway (fB(-/-) mice) had significantly less impact on injury profiles. Consequently, the effect of a targeted inhibitor of the alternative pathway was investigated in a therapeutic protocol. Following the establishment of colitis, mice were treated with CR2-fH during subsequent periods of DSS treatment and acute injury (modelling relapse). CR2-fH significantly reduced complement activation, inflammation and injury in the colon, and additionally reduced fibrosis. Alternative pathway inhibition also altered the immune response in the chronic state in terms of reducing numbers of B cells, macrophages and mature dendritic cells in the lamina propria. This study indicates an important role for the alternative pathway of complement in the pathogenesis and the shaping of an immune response in chronic DSS-induced colitis, and supports further investigation into the use of targeted alternative pathway inhibition for the treatment of IBD.
机构:
Johns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA
Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USAJohns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA
Alex, Philip
;
Zachos, Nicholas C.
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机构:
Johns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USAJohns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA
Zachos, Nicholas C.
;
Nguyen, Thuan
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h-index: 0
机构:
Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USAJohns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA
Nguyen, Thuan
;
Gonzales, Liberty
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机构:
Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USAJohns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA
Gonzales, Liberty
;
Chen, Tian-E
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h-index: 0
机构:
Johns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USAJohns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA
Chen, Tian-E
;
Conklin, Laurie S.
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h-index: 0
机构:
Johns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USAJohns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA
Conklin, Laurie S.
;
Centola, Michoel
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Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USAJohns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA
Centola, Michoel
;
Li, Xuhang
论文数: 0引用数: 0
h-index: 0
机构:
Johns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USAJohns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA
机构:
Shiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Osaka Med Coll, Dept Pediat, Takatsuki, Osaka 5690801, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Aomatsu, Tomoki
;
Imaeda, Hirotsugu
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h-index: 0
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Shiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Imaeda, Hirotsugu
;
Takahashi, Kenichiro
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h-index: 0
机构:
Shiga Univ Med Sci, Grad Sch, Div Mucosal Immunol, Otsu, Shiga 5202192, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Takahashi, Kenichiro
;
Fujimoto, Takehide
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h-index: 0
机构:
Shiga Univ Med Sci, Grad Sch, Div Mucosal Immunol, Otsu, Shiga 5202192, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Fujimoto, Takehide
;
Kasumi, Eiji
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机构:
Shiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Kasumi, Eiji
;
Ban, Hiromitsu
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机构:
Shiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Ban, Hiromitsu
;
Bamba, Shigeki
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机构:
Shiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Bamba, Shigeki
;
Yoden, Atsushi
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机构:
Osaka Med Coll, Dept Pediat, Takatsuki, Osaka 5690801, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Yoden, Atsushi
;
Tamai, Hiroshi
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机构:
Osaka Med Coll, Dept Pediat, Takatsuki, Osaka 5690801, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Tamai, Hiroshi
;
Fujiyama, Yoshihide
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h-index: 0
机构:
Shiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Fujiyama, Yoshihide
;
Andoh, Akira
论文数: 0引用数: 0
h-index: 0
机构:
Shiga Univ Med Sci, Grad Sch, Div Mucosal Immunol, Otsu, Shiga 5202192, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
机构:Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA
Atkinson, C
;
Song, HB
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机构:Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA
Song, HB
;
Lu, B
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机构:Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA
Lu, B
;
Qiao, F
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机构:Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA
Qiao, F
;
Burns, TA
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机构:Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA
Burns, TA
;
Holers, VM
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机构:Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA
Holers, VM
;
Tsokos, GC
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机构:Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA
Tsokos, GC
;
Tomlinson, S
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Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USAMed Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA
机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Chen, Guojiang
;
Yang, Yuemei
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机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Tianjin Univ, Dept Mol & Cellular Pharmacol, Coll Pharmaceut Sci & Technol, Tianjin, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Yang, Yuemei
;
Gao, Xudong
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机构:
Tianjin Univ, Dept Mol & Cellular Pharmacol, Coll Pharmaceut Sci & Technol, Tianjin, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Gao, Xudong
;
Dou, Yan
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机构:
Gen Hosp PLA, Dept Gastroenterol, Beijing, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Dou, Yan
;
Wang, Huihui
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机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Inner Mongolia Med Coll, Ctr Mol Biol, Hohhot, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Wang, Huihui
;
Han, Gencheng
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机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Han, Gencheng
;
Wang, Renxi
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机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Wang, Renxi
;
Wang, Jianan
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机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Wang, Jianan
;
Wang, Liyan
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Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Wang, Liyan
;
Li, Xinying
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Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Li, Xinying
;
Guo, Renfeng
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机构:
InflaRx GmbH, Jena, GermanyInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Guo, Renfeng
;
Xiao, He
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h-index: 0
机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Xiao, He
;
Shen, Beifen
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机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Shen, Beifen
;
Li, Yan
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h-index: 0
机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
机构:
Johns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA
Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USAJohns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA
Alex, Philip
;
Zachos, Nicholas C.
论文数: 0引用数: 0
h-index: 0
机构:
Johns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USAJohns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA
Zachos, Nicholas C.
;
Nguyen, Thuan
论文数: 0引用数: 0
h-index: 0
机构:
Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USAJohns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA
Nguyen, Thuan
;
Gonzales, Liberty
论文数: 0引用数: 0
h-index: 0
机构:
Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USAJohns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA
Gonzales, Liberty
;
Chen, Tian-E
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h-index: 0
机构:
Johns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USAJohns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA
Chen, Tian-E
;
Conklin, Laurie S.
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h-index: 0
机构:
Johns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USAJohns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA
Conklin, Laurie S.
;
Centola, Michoel
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h-index: 0
机构:
Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USAJohns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA
Centola, Michoel
;
Li, Xuhang
论文数: 0引用数: 0
h-index: 0
机构:
Johns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USAJohns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA
机构:
Shiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Osaka Med Coll, Dept Pediat, Takatsuki, Osaka 5690801, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Aomatsu, Tomoki
;
Imaeda, Hirotsugu
论文数: 0引用数: 0
h-index: 0
机构:
Shiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Imaeda, Hirotsugu
;
Takahashi, Kenichiro
论文数: 0引用数: 0
h-index: 0
机构:
Shiga Univ Med Sci, Grad Sch, Div Mucosal Immunol, Otsu, Shiga 5202192, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Takahashi, Kenichiro
;
Fujimoto, Takehide
论文数: 0引用数: 0
h-index: 0
机构:
Shiga Univ Med Sci, Grad Sch, Div Mucosal Immunol, Otsu, Shiga 5202192, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Fujimoto, Takehide
;
Kasumi, Eiji
论文数: 0引用数: 0
h-index: 0
机构:
Shiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Kasumi, Eiji
;
Ban, Hiromitsu
论文数: 0引用数: 0
h-index: 0
机构:
Shiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Ban, Hiromitsu
;
Bamba, Shigeki
论文数: 0引用数: 0
h-index: 0
机构:
Shiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Bamba, Shigeki
;
Yoden, Atsushi
论文数: 0引用数: 0
h-index: 0
机构:
Osaka Med Coll, Dept Pediat, Takatsuki, Osaka 5690801, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Yoden, Atsushi
;
Tamai, Hiroshi
论文数: 0引用数: 0
h-index: 0
机构:
Osaka Med Coll, Dept Pediat, Takatsuki, Osaka 5690801, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Tamai, Hiroshi
;
Fujiyama, Yoshihide
论文数: 0引用数: 0
h-index: 0
机构:
Shiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
Fujiyama, Yoshihide
;
Andoh, Akira
论文数: 0引用数: 0
h-index: 0
机构:
Shiga Univ Med Sci, Grad Sch, Div Mucosal Immunol, Otsu, Shiga 5202192, JapanShiga Univ Med Sci, Grad Sch, Dept Med, Otsu, Shiga 5202192, Japan
机构:Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA
Atkinson, C
;
Song, HB
论文数: 0引用数: 0
h-index: 0
机构:Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA
Song, HB
;
Lu, B
论文数: 0引用数: 0
h-index: 0
机构:Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA
Lu, B
;
Qiao, F
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h-index: 0
机构:Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA
Qiao, F
;
Burns, TA
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h-index: 0
机构:Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA
Burns, TA
;
Holers, VM
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h-index: 0
机构:Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA
Holers, VM
;
Tsokos, GC
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h-index: 0
机构:Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA
Tsokos, GC
;
Tomlinson, S
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h-index: 0
机构:
Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USAMed Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA
机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Chen, Guojiang
;
Yang, Yuemei
论文数: 0引用数: 0
h-index: 0
机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Tianjin Univ, Dept Mol & Cellular Pharmacol, Coll Pharmaceut Sci & Technol, Tianjin, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Yang, Yuemei
;
Gao, Xudong
论文数: 0引用数: 0
h-index: 0
机构:
Tianjin Univ, Dept Mol & Cellular Pharmacol, Coll Pharmaceut Sci & Technol, Tianjin, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Gao, Xudong
;
Dou, Yan
论文数: 0引用数: 0
h-index: 0
机构:
Gen Hosp PLA, Dept Gastroenterol, Beijing, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Dou, Yan
;
Wang, Huihui
论文数: 0引用数: 0
h-index: 0
机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Inner Mongolia Med Coll, Ctr Mol Biol, Hohhot, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Wang, Huihui
;
Han, Gencheng
论文数: 0引用数: 0
h-index: 0
机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Han, Gencheng
;
Wang, Renxi
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h-index: 0
机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Wang, Renxi
;
Wang, Jianan
论文数: 0引用数: 0
h-index: 0
机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Wang, Jianan
;
Wang, Liyan
论文数: 0引用数: 0
h-index: 0
机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Wang, Liyan
;
Li, Xinying
论文数: 0引用数: 0
h-index: 0
机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Li, Xinying
;
Guo, Renfeng
论文数: 0引用数: 0
h-index: 0
机构:
InflaRx GmbH, Jena, GermanyInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Guo, Renfeng
;
Xiao, He
论文数: 0引用数: 0
h-index: 0
机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Xiao, He
;
Shen, Beifen
论文数: 0引用数: 0
h-index: 0
机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
Shen, Beifen
;
Li, Yan
论文数: 0引用数: 0
h-index: 0
机构:
Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R ChinaInst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China