Group 2 Innate Lymphoid Cells Exhibit Tissue-Specific Dynamic Behaviour During Type 2 Immune Responses.

Laurence S C Lok,Seth T Scanlon,Padraic G Fallon,Helen E Jolin,Masaru Ishii,Jennifer A Walker,Menna R Clatworthy,Andrew N J Mckenzie

doi:10.3389/fimmu.2021.711907

Abstract

Group 2 innate lymphoid cells (ILC2s) are early effectors of mucosal type 2 immunity, producing cytokines such as interleukin (IL)-13 to mediate responses to helminth infection and allergen-induced inflammation. ILC2s are also present in lymph nodes (LNs) and can express molecules required for antigen presentation, but to date there are limited data on their dynamic behaviour. We used a CD2/IL-13 dual fluorescent reporter mouse for in vivo imaging of ILC2s and Th2 T cells in real time following a type 2 priming helminth infection or egg injection. After helminth challenge, we found that ILC2s were the main source of IL-13 in lymphoid organs (Peyer’s patches and peripheral LNs), and were located in T cell areas. Intravital imaging demonstrated an increase in IL-13+ ILC2 size and movement following helminth infection, but reduced duration of interactions with T cells compared with those in homeostasis. In contrast, in the intestinal mucosa, we observed an increase in ILC2-T cell interactions post-infection, including some of prolonged duration, as well as increased IL-13+ ILC2 movement. These data suggest that ILC2 activation enhances cell motility, with the potential to increase the area of distribution of cytokines to optimise the early generation of type 2 responses. The prolonged ILC2 interactions with T cells within the intestinal mucosa are consistent with the conclusion that contact-based T cell activation may occur within inflamed tissues rather than lymphoid organs. Our findings have important implications for our understanding of the in vivo biology of ILC2s and the way in which these cells facilitate adaptive immune responses.

Highlights

Group 2 innate lymphoid cells (ILC2s), a relatively recently characterised ILC subset [1,2,3], are effectors of type 2 immunity
In order to visualise ILC2s in vivo we used CD2-green fluorescent protein (GFP)/IL-13tdTomato reporter mice, in which T cells were CD2+ (GFP+), Th2 cells CD2+IL-13+ (GFP+tdTomato+) and ILC2s CD2negIL13+, allowing ILC2s to be distinguished from Th2 cells, with CD2+IL-13neg T cells acting as in vivo controls
Flow cytometric analysis of lymphoid tissues confirmed that IL13+ cells were LinnegSiglec-FnegCD2negIL-7Ra+ICOS+ ILC2s (Figures S1A, B), which were negative for CD3 (Figure S1C)

Summary

Introduction

Group 2 innate lymphoid cells (ILC2s), a relatively recently characterised ILC subset [1,2,3], are effectors of type 2 immunity. In helminth infection and allergic inflammation, ILC2s are early responders to epithelium-derived tissue alarmins, interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP), producing type 2 cytokines including IL-5 and IL-13 [3,4,5]. Following infection with Nippostrongylus brasiliensis, a helminth frequently used to study type 2 immunity, ILC2-derived IL-13 is critical for worm expulsion from the gut [3, 6]. Following N. brasiliensis infection, the main early source of IL13 was shown to be from migratory inflammatory ILC2s not tissue resident ILC2s [11]. Inflammatory ILC2s may be a short-lived subset that migrates from tissues following infection to act as early source of type 2 cytokines. ILC2s have been implicated in the pathogenesis of allergic diseases, asthma, with increased ILC2 numbers observed in the airways of asthmatics [13, 14]

Methods

Results

Conclusion