Expansion of parasite-specific CD4+ and CD8+ T cells expressing IL-10 superfamily cytokine members and their regulation in human lymphatic filariasis.
Expansion of parasite-specific CD4+ and CD8+ T cells expressing IL-10 superfamily cytokine members and their regulation in human lymphatic filariasis.
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表达IL-10超家族细胞因子成员的寄生虫特异性CD4+和CD8+ T细胞的膨胀及其在人淋巴丝虫病中的调节。
DOI：
10.1371/journal.pntd.0002762
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发表时间：
2014-04
影响因子：
3.8
通讯作者：
Babu S
中科院分区：
文献类型：
--
作者：
Anuradha R;George PJ;Hanna LE;Kumaran P;Chandrasekaran V;Nutman TB;Babu S
淋巴丝虫病（LF）已知与IL-10的产生增加有关。其他IL-10家族成员在感染和/或疾病发病机制中的作用尚不清楚。我们检测了LF中IL-10家族成员IL-19、IL-24和IL-26的表达模式。我们证明，CD 4+和CD 8 + T细胞表达IL-19，IL-24和IL-26和表达IL-19和IL-24（以及IL-10）的CD 4 + T细胞的频率显着增加，在基线和丝虫抗原刺激后，与丝虫性水肿和未感染的个体相比，LF患者。这种CD 4 + T细胞表达模式与丝虫抗原刺激的PBMC产生的IL-19和IL-24增加有关。此外，表达IL-26的CD 4+和CD 8 + T细胞的频率在丝虫抗原刺激后在丝虫性水肿个体中显著增加。有趣的是，IL-10阻断导致IL-19+和IL-24+ T细胞的频率降低，而添加重组IL-10导致IL-19+和IL-24+ T细胞的频率显著增加以及IL-19和IL-24基因表达显著上调，表明IL-10调节T细胞中IL-19和IL-24的表达。此外，IL-1β和IL-23阻断还诱导IL-19+和IL-24+ T细胞的频率降低，表明这些细胞因子在诱导表达IL-19和IL-24的T细胞中具有新的作用。最后，感染的消除导致表达IL-10、IL-19和IL-24的抗原特异性CD 4 + T细胞的频率显著降低。因此，我们的研究结果表明，IL-19和IL-24与活动性丝虫感染的免疫应答调节相关，并可能与预防病理发展相关，而IL-26主要与LF的病理相关。淋巴丝虫病困扰着全世界超过1.2亿人。虽然这种感染大多数在临床上没有症状，但约有4 000万人患有明显的病态临床病理学，其特征是阴囊区和下肢肿胀（鞘膜积液和水肿）。影响这些个体疾病发病机制的宿主免疫因素尚未完全了解。已知CD 4+和CD 8 + T细胞通过分泌促炎细胞因子在促进发病机制中发挥作用，而已知IL-10在抑制炎症中发挥重要作用。IL-10属于细胞因子家族，包括IL-19、IL-24和IL-26，称为IL-10超家族。我们研究了这些细胞因子在无症状感染和无临床病理学的个体以及具有明显临床病理学的个体中是否具有与IL-10相似的功能。我们首先确定了CD 4+和CD 8 + T细胞产生这些细胞因子。接下来，我们鉴定了分泌IL-19和IL-24的T细胞与无症状感染的显著关联。相比之下，分泌IL-26的T细胞似乎与丝虫感染中淋巴病理的存在显著相关。因此，我们发现了一个潜在的新的调节途径，涉及IL-10超家族细胞因子在丝虫感染。
Lymphatic filariasis (LF) is known to be associated with an increased production of IL-10. The role of the other IL-10 family members in the pathogenesis of infection and/or disease is not known. We examined the expression patterns of IL-10 family members – IL-19, IL-24 and IL-26 in LF. We demonstrate that both CD4+ and CD8+ T cells express IL-19, IL-24 and IL-26 and that the frequency of CD4+ T cells expressing IL-19 and IL-24 (as well as IL-10) is significantly increased at baseline and following filarial antigen stimulation in patients with LF in comparison to individuals with filarial lymphedema and uninfected individuals. This CD4+ T cell expression pattern was associated with increased production of IL-19 and IL-24 by filarial – antigen stimulated PBMC. Moreover, the frequency of CD4+ and CD8+ T cells expressing IL-26 was significantly increased following filarial antigen stimulation in filarial lymphedema individuals. Interestingly, IL-10 blockade resulted in diminished frequencies of IL-19+ and IL-24+ T cells, whereas the addition of recombinant IL-10 resulted in significantly increased frequency of IL-19+ and IL-24+ T cells as well as significantly up regulated IL-19 and IL-24 gene expression, suggesting that IL-10 regulates IL-19 and IL-24 expression in T cells. In addition, IL-1β and IL-23 blockade also induced a diminution in the frequency of IL-19+ and IL-24+ T cells, indicating a novel role for these cytokines in the induction of IL-19 and IL-24 expressing T cells. Finally, elimination of infection resulted in significantly decreased frequencies of antigen – specific CD4+ T cells expressing IL-10, IL-19 and IL-24. Our findings, therefore, suggest that IL-19 and IL-24 are associated with the regulation of immune responses in active filarial infection and potentially with protection against development of pathology, while IL-26 is predominantly associated with pathology in LF. Lymphatic filariasis afflicts over 120 million people worldwide. While the infection is mostly clinically asymptomatic, approximately 40 million people suffer from overt, morbid clinical pathology, characterized by swelling of the scrotal area and lower limbs (hydrocele and lymphedema). Host immunologic factors that influence the pathogenesis of disease in these individuals are not completely understood. CD4+ and CD8+ T cells are known to play a role in promoting pathogenesis through the secretion of pro-inflammatory cytokines, while IL-10 is known to play an important role in dampening inflammation. IL-10 belongs to a family of cytokines that include IL-19, IL-24 and IL-26, known as the IL-10 superfamily. We investigated whether these cytokines have a function similar to IL-10 in individuals with asymptomatic infection and no clinical pathology and those with overt, clinical pathology. We first identify that CD4+ and CD8+ T cells produce these cytokines. We next identify a significant association of IL-19 and IL-24 secreting T cells with asymptomatic infection. IL-26 secreting T cells, in contrast, appear to be significantly associated with the presence of lymphatic pathology in filarial infection. Therefore, we have uncovered a potentially new regulatory pathway involving the IL-10 superfamily cytokines in filarial infections.
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影响因子：
6.7
作者：
Anuradha R;George PJ;Pavan Kumar N;Fay MP;Kumaraswami V;Nutman TB;Babu S
通讯作者：
Babu S
影响因子：
82.9
作者：
Ghoreschi, K;Thomas, P;Röcken, M
通讯作者：
Röcken, M
DOI：
10.1084/jem.20060244
发表时间：
2006-11-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chan JR;Blumenschein W;Murphy E;Diveu C;Wiekowski M;Abbondanzo S;Lucian L;Geissler R;Brodie S;Kimball AB;Gorman DM;Smith K;de Waal Malefyt R;Kastelein RA;McClanahan TK;Bowman EP
通讯作者：
Bowman EP
MDA-7/IL-24：IL-10基因家族的独特成员，促进了以癌为靶向的毒性。
影响因子：
13
作者：
Dash, Rupesh;Bhutia, Sujit K.;Azab, Belal;Su, Zhao-zhong;Quinn, Bridget A.;Kegelmen, Timothy P.;Das, Swadesh K.;Kim, Keetae;Lee, Seok-Geun;Park, Margaret A.;Yacoub, Adly;Rahmani, Mohammed;Emdad, Luni;Dmitriev, Igor P.;Wang, Xiang-Yang;Sarkar, Devanand;Grant, Steven;Dent, Paul;Curiel, David T.;Fisher, Paul B.
通讯作者：
Fisher, Paul B.
影响因子：
15.9
作者：
NUTMAN, TB;KUMARASWAMI, V;OTTESEN, EA
通讯作者：
OTTESEN, EA