Nature：对小肠细菌的免疫反应

最近被定性的“先天淋巴细胞”(ILCs) 在功能上可被划分成三类。第一类的ILCs 产生干扰素-γ；第二类的ILCs 表达白介素-5、白介素-13和双调蛋白；第三类的ILCs 产生白介素-17A和白介素-22。ILCs在适应性免疫存在时的功能及它们影响适应性免疫细胞反应的潜力在很大程度上是不知道的。现在用小鼠所做的一项研究显示，第三类的ILCs处理和呈现抗原，并通过一个依赖于“MHC-class-II”的机制控制CD4+ T-细胞对小肠共生菌的反应。这一发现也许有助于了解与对共生菌的炎性宿主免疫反应相关的人类慢性病的病理。

Nature  doi: 10.1038/nature12240

Innate lymphoid cells regulate CD4⁺ T-cell responses to intestinal commensal bacteria

Matthew R. Hepworth,Laurel A. Monticelli, Thomas C. Fung,Carly G. K. Ziegler,Stephanie Grunberg,Rohini Sinha,Adriana R. Mantegazza,Hak-Ling Ma, Alison Crawford, Jill M. Angelosanto,E. John Wherry,Pandelakis A. Koni,Frederic D. Bushman,Charles O. Elson, Gérard Eberl,David Artis& Gregory F. Sonnenberg

Innate lymphoid cells (ILCs) are a recently characterized family of immune cells that have critical roles in cytokine-mediated regulation of intestinal epithelial cell barrier integrity. Alterations in ILC responses are associated with multiple chronic human diseases, including inflammatory bowel disease, implicating a role for ILCs in disease pathogenesis. Owing to an inability to target ILCs selectively, experimental studies assessing ILC function have predominantly used mice lacking adaptive immune cells. However, in lymphocyte-sufficient hosts ILCs are vastly outnumbered by CD4⁺ T cells, which express similar profiles of effector cytokines. Therefore, the function of ILCs in the presence of adaptive immunity and their potential to influence adaptive immune cell responses remain unknown. To test this, we used genetic or antibody-mediated depletion strategies to target murine ILCs in the presence of an adaptive immune system. We show that loss of retinoic-acid-receptor-related orphan receptor-γt-positive (RORγt⁺) ILCs was associated with dysregulated adaptive immune cell responses against commensal bacteria and low-grade systemic inflammation. Remarkably, ILC-mediated regulation of adaptive immune cells occurred independently of interleukin (IL)-17A, IL-22 or IL-23. Genome-wide transcriptional profiling and functional analyses revealed that RORγt⁺ ILCs express major histocompatibility complex class II (MHCII) and can process and present antigen. However, rather than inducing T-cell proliferation, ILCs acted to limit commensal bacteria-specific CD4⁺ T-cell responses. Consistent with this, selective deletion of MHCII in murine RORγt⁺ ILCs resulted in dysregulated commensal bacteria-dependent CD4⁺ T-cell responses that promoted spontaneous intestinal inflammation. These data identify that ILCs maintain intestinal homeostasis through MHCII-dependent interactions with CD4⁺ T cells that limit pathological adaptive immune cell responses to commensal bacteria.