Differential requirement for P2X7R function in IL-17 dependent vs. IL-17 independent cellular immune responses.
Differential requirement for P2X7R function in IL-17 dependent vs. IL-17 independent cellular immune responses.
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DOI：
10.1111/ajt.12741
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发表时间：
2014-07
期刊：
影响因子：
--
通讯作者：
Burlingham WJ
中科院分区：
文献类型：
--
作者：
Sullivan JA;Jankowska-Gan E;Shi L;Roenneburg D;Hegde S;Greenspan DS;Wilkes DS;Denlinger LC;Burlingham WJ
对V型胶原蛋白（Col V）的IL 17依赖性自身免疫与肺移植闭塞性细支气管炎相关。与对破伤风类毒素（TT）的Th-1依赖性免疫应答不同，肺移植患者中对Col V的Th 17应答及其在冠状动脉疾病患者中观察到的Th 1/17变体需要IL-1β、TNFα和CD 14+细胞。鉴于P2 X7 R参与单核细胞IL-1β应答，我们研究了其在Th 17、Th 1/17和Th 1介导的促炎应答中的作用。将来自Col V反应性患者的抗原脉冲的PBMC与P2 X7 R拮抗剂一起转移到SCID小鼠足垫沿着中，揭示了对Col V特异性肿胀反应的选择性抑制，但对TT特异性肿胀反应没有抑制。P2 X7 R抑制剂阻断单核细胞的IL-1β诱导，包括Col V-α1肽诱导的（T依赖性）以及天然Col V诱导的（T非依赖性）应答。P2 X7 R在PBMC中CXCR 3 + CCR 4 +/6+ CD 4 + [Th 17]亚群上的表达显著高于CXCR 3 + CCR 4/6-CD 4 + [Th 1]亚群，表明对P2 X7 R的选择性依赖可能超出了Col V自身免疫。事实上，P2 X7 R抑制剂在心脏移植患者中不仅抑制抗Col V，而且抑制Th 1/17介导的同种免疫，而不影响抗病毒EBV应答。这些结果表明，靶向P2 X7 R的药物可能有效地治疗Th 17相关的移植病理，同时维持Th 1对感染的免疫力。
IL17-dependent autoimmunity to Collagen type V (Col V) has been associated with lung transplant obliterative bronchiolitis. Unlike the Th-1-dependent immune responses to tetanus toxoid (TT), the Th17 response to Col V in lung transplant patients and its Th1/17 variant observed in coronary artery disease patients requires IL-1β, TNFα and CD14+ cells. Given the involvement of the P2X7R in monocyte IL-1β responses, we investigated its role in Th17, Th1/17, and Th1- mediated pro-inflammatory responses. Transfer of antigen-pulsed PBMC from Col V -reactive patients into SCID mouse footpads along with P2X7R antagonists revealed a selective inhibition of Col V-, but not TT -specific swelling responses. P2X7R inhibitors blocked IL-1β induction from monocytes, including both Col V-α1 peptide-induced (T-dependent), as well as native Col V induced (T-independent) responses. Significantly higher P2X7R expression was found on CXCR3negCCR4+/6+ CD4+ [Th17] vs. CXCR3+CCR4/6neg CD4+ [Th1] subsets in PBMC, suggesting that the paradigm of selective dependence on P2X7R might extend beyond Col V autoimmunity. Indeed, P2X7R inhibitors suppressed not only anti-Col V, but also Th1/17–mediated allo-immunity, in a heart transplant patient without affecting anti-viral EBV responses. These results suggest that agents targeting the P2X7R might effectively treat Th17-related transplant pathologies, while maintaining Th1-immunity to infection.
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DOI：
10.1084/jem.20070663
发表时间：
2007-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Annunziato F;Cosmi L;Santarlasci V;Maggi L;Liotta F;Mazzinghi B;Parente E;Filì L;Ferri S;Frosali F;Giudici F;Romagnani P;Parronchi P;Tonelli F;Maggi E;Romagnani S
通讯作者：
Romagnani S
影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
20.1
作者：
Dart ML;Jankowska-Gan E;Huang G;Roenneburg DA;Keller MR;Torrealba JR;Rhoads A;Kim B;Bobadilla JL;Haynes LD;Wilkes DS;Burlingham WJ;Greenspan DS
通讯作者：
Greenspan DS
影响因子：
15.9
作者：
Hyman, Matthew C.;Petrovic-Djergovic, Danica;Pinsky, David J.
通讯作者：
Pinsky, David J.
DOI：
10.1152/ajpcell.2000.279.4.c1189
发表时间：
2000-10-01
影响因子：
5.5
作者：
Gu, BJ;Zhang, WY;Wiley, JS
通讯作者：
Wiley, JS