The alarmin IL33 orchestrates type 2 immune-mediated control of thymus regeneration.
The alarmin IL33 orchestrates type 2 immune-mediated control of thymus regeneration.
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DOI：
10.1038/s41467-023-43072-x
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发表时间：
2023-11-08
影响因子：
16.6
通讯作者：
Anderson, Graham
中科院分区：
文献类型：
--
作者：
Cosway, Emilie J.;James, Kieran D.;White, Andrea J.;Parnell, Sonia M.;Bacon, Andrea;Mckenzie, Andrew N. J.;Jenkinson, W. E.;Anderson, Graham
作为t细胞发育的主要部位，胸腺决定了宿主的免疫能力。胸腺功能的速率不是恒定的，胸腺再生对于环境因素和治疗干预造成的组织损伤后恢复新t细胞的产生至关重要。在这里，我们发现白细胞介素（IL） 33是鳞状细胞1+胸腺间质的产物，通过2型先天免疫网络对胸腺再生既必要又充分。IL33刺激产生il5的2型先天淋巴样细胞（ILC2）的扩张，从而触发胸腺内IL4可用性的细胞开关。这使得嗜酸性粒细胞il - 4的产生能够在诱导胸腺生成的上皮细胞室恢复之前重建胸腺间质。总之，我们确定了2型先天免疫的正反馈机制，该机制调节组织损伤后胸腺功能的恢复。虽然胸腺功能随着年龄的增长而下降，但胸腺在损伤后也有再生的能力。在这里，作者证明了IL-33和2型先天淋巴细胞在辐射损伤后触发嗜酸性粒细胞的扩张，这反过来又产生IL-4来刺激胸腺再生过程中胸腺间质的恢复。
As the primary site of T-cell development, the thymus dictates immune competency of the host. The rates of thymus function are not constant, and thymus regeneration is essential to restore new T-cell production following tissue damage from environmental factors and therapeutic interventions. Here, we show the alarmin interleukin (IL) 33 is a product of Sca1+ thymic mesenchyme both necessary and sufficient for thymus regeneration via a type 2 innate immune network. IL33 stimulates expansion of IL5-producing type 2 innate lymphoid cells (ILC2), which triggers a cellular switch in the intrathymic availability of IL4. This enables eosinophil production of IL4 to re-establish thymic mesenchyme prior to recovery of thymopoiesis-inducing epithelial compartments. Collectively, we identify a positive feedback mechanism of type 2 innate immunity that regulates the recovery of thymus function following tissue injury. Although thymic function declines with age, the thymus also has the ability to regenerate following injury. Here, the authors demonstrate that IL-33 and type-2 innate lymphoid cells trigger the expansion of eosinophils following radiation injury, which in turn produce IL-4 to stimulate the recovery of the thymus mesenchyme during thymus regeneration.
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影响因子：
24.8
作者：
Jou E;Rodriguez-Rodriguez N;Ferreira AF;Jolin HE;Clark PA;Sawmynaden K;Ko M;Murphy JE;Mannion J;Ward C;Matthews DJ;Buczacki SJA;McKenzie ANJ
通讯作者：
McKenzie ANJ
影响因子：
24.8
作者：
Cosway EJ;White AJ;Parnell SM;Schweighoffer E;Jolin HE;Bacon A;Rodewald HR;Tybulewicz V;McKenzie ANJ;Jenkinson WE;Anderson G
通讯作者：
Anderson G
DOI：
10.1126/science.1218004
发表时间：
2012-04-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Dudakov JA;Hanash AM;Jenq RR;Young LF;Ghosh A;Singer NV;West ML;Smith OM;Holland AM;Tsai JJ;Boyd RL;van den Brink MR
通讯作者：
van den Brink MR
DOI：
10.1073/pnas.1304046110
发表时间：
2013-06-11
影响因子：
11.1
作者：
Goh, Y. P. Sharon;Henderson, Neil C.;Chawla, Ajay
通讯作者：
Chawla, Ajay
影响因子：
2.7
作者：
AUERBACH, R
通讯作者：
AUERBACH, R