CD161 expression characterizes a subpopulation of human regulatory T cells that produces IL-17 in a STAT3-dependent manner.
CD161 expression characterizes a subpopulation of human regulatory T cells that produces IL-17 in a STAT3-dependent manner.
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DOI：
10.1002/eji.201243296
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发表时间：
2013-08
影响因子：
5.4
通讯作者：
Lombardi, Giovanna
中科院分区：
文献类型：
--
作者：
Afzali, Behdad;Mitchell, Peter J.;Edozie, Francis C.;Povoleri, Giovanni A. M.;Dowson, Sophie E.;Demandt, Laura;Walter, Gina;Canavan, James B.;Scotta, Cristiano;Menon, Bina;Chana, Prabhjoat S.;Khamri, Wafa;Kordasti, Shahram Y.;Heck, Susanne;Grimbacher, Bodo;Tree, Timothy;Cope, Andrew P.;Taams, Leonie S.;Lechler, Robert I.;John, Susan;Lombardi, Giovanna
Treg细胞对于预防自身免疫性疾病至关重要，因此是基于细胞的临床治疗的主要候选者。然而，人Treg细胞是“可塑性的”，并且能够在炎症条件下产生IL-17。在这里，我们鉴定和表征了可以被诱导产生IL-17的人Treg亚群，并鉴定了其机制。我们证实，人Treg细胞亚群在IL-1β存在下活化时在体外产生IL-17，但不产生IL-6。“IL-17潜力”限于表达自然杀伤细胞标志物CD 161的群体III（CD 4 + CD 25 hiCD 127 loCD 45 RA-）Treg细胞。我们表明，这些细胞在功能上是抑制性的，并具有与其他Treg细胞亚群相似的表型/分子特征，并在IL-17诱导后保留其抑制功能。重要的是，我们发现IL-17的产生是STAT 3依赖性的，来自STAT 3突变患者的Treg细胞不能产生IL-17。最后，我们发现CD 161+群体III Treg细胞在炎性关节炎患者的炎症关节中积累，并且是这些部位的主要IL-17产生Treg细胞群体。由于来自该Treg细胞亚群的IL-17产生不伴随调节功能的丧失，因此在细胞治疗的情况下，从细胞产物中排除这些细胞可能是不必要的。
Treg cells are critical for the prevention of autoimmune diseases and are thus prime candidates for cell-based clinical therapy. However, human Treg cells are “plastic”, and are able to produce IL-17 under inflammatory conditions. Here, we identify and characterize the human Treg subpopulation that can be induced to produce IL-17 and identify its mechanisms. We confirm that a subpopulation of human Treg cells produces IL-17 in vitro when activated in the presence of IL-1β, but not IL-6. “IL-17 potential” is restricted to population III (CD4+CD25hiCD127loCD45RA−) Treg cells expressing the natural killer cell marker CD161. We show that these cells are functionally as suppressive and have similar phenotypic/molecular characteristics to other subpopulations of Treg cells and retain their suppressive function following IL-17 induction. Importantly, we find that IL-17 production is STAT3 dependent, with Treg cells from patients with STAT3 mutations unable to make IL-17. Finally, we show that CD161+ population III Treg cells accumulate in inflamed joints of patients with inflammatory arthritis and are the predominant IL-17-producing Treg-cell population at these sites. As IL-17 production from this Treg-cell subpopulation is not accompanied by a loss of regulatory function, in the context of cell therapy, exclusion of these cells from the cell product may not be necessary.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
人白细胞介素17产生的细胞起源于CD161+ CD4+ T细胞前体。
影响因子：
15.3
作者：
Cosmi, Lorenzo;De Palma, Raffaele;Santarlasci, Veronica;Maggi, Laura;Capone, Manuela;Frosali, Francesca;Rodolico, Gabriella;Querci, Valentina;Abbate, Gianfranco;Angeli, Roberta;Berrino, Liberato;Fambrini, Massimiliano;Caproni, Marzia;Tonelli, Francesco;Lazzeri, Elena;Parronchi, Paola;Liotta, Francesco;Maggi, Enrico;Romagnani, Sergio;Annunziato, Francesco
通讯作者：
Annunziato, Francesco
DOI：
10.1084/jem.20080218
发表时间：
2008-07-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ma CS;Chew GY;Simpson N;Priyadarshi A;Wong M;Grimbacher B;Fulcher DA;Tangye SG;Cook MC
通讯作者：
Cook MC
影响因子：
16.2
作者：
Marek-Trzonkowska N;Mysliwiec M;Dobyszuk A;Grabowska M;Techmanska I;Juscinska J;Wujtewicz MA;Witkowski P;Mlynarski W;Balcerska A;Mysliwska J;Trzonkowski P
通讯作者：
Trzonkowski P
影响因子：
4.4
作者：
Baecher-Allan, Clare;Wolf, Elizabeth;Haller, David A.
通讯作者：
Haller, David A.