Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
Immunity. 2012 Sep 21;37(3):463-74. doi: 10.1016/j.immuni.2012.06.012. Epub 2012 Sep 13.
Natural helper (NH) cells are innate lymphoid cells (ILCs) that produce T helper-2 (Th2)-cell-type cytokines in the lung- and gut-associated lymphoid tissues. Currently, the lineage relationship between NH cells in different tissues and between NH cells and interleukin-22 (IL-22)-producing retinoic-acid-receptor-related orphan receptor (ROR)γt-positive ILCs is unclear. Here, we report that NH cells express RORα, but not RORγt. RORα-deficient, but not RORγt-deficient, mice lacked NH cells in all tissues, whereas all other lymphocytes, including RORγt(+) ILCs, were unaffected. NH-cell-deficient mice generated by RORα-deficient bone-marrow transplantation had normal Th2 cell responses but failed to develop acute lung inflammation in response to protease allergen, thus confirming the essential role of NH cells in allergic lung inflammation. We have also identified RORα-dependent NH cell progenitors in the bone marrow. Thus, all NH cells belong to a unique RORα-dependent cell lineage separate from other lymphoid cell lineages.
自然helper（NH）细胞是先天淋巴细胞（ILCs），它们在肺和肠道相关淋巴组织中产生 T 辅助-2（Th2）-细胞型细胞因子。目前，不同组织中 NH 细胞之间以及 NH 细胞与产生白细胞介素-22（IL-22）的视黄酸受体相关孤儿受体（ROR）γt阳性 ILCs 之间的谱系关系尚不清楚。在这里，我们报告 NH 细胞表达 RORα，但不表达 RORγt。RORα 缺陷但不是 RORγt 缺陷的小鼠在所有组织中都缺乏 NH 细胞，而所有其他淋巴细胞，包括 RORγt(+) ILCs，均不受影响。通过 RORα 缺陷骨髓移植产生的 NH 细胞缺陷小鼠具有正常的 Th2 细胞反应，但对蛋白酶过敏原无急性肺炎症反应，从而证实 NH 细胞在过敏性肺炎症中的重要作用。我们还在骨髓中鉴定了 RORα 依赖性 NH 细胞前体。因此，所有 NH 细胞都属于独特的 RORα 依赖性细胞谱系，与其他淋巴细胞谱系不同。
