Abstract
Innate lymphoid cells (ILCs) contribute to host defence and tissue repair but can induce immunopathology. Recent work has revealed tissue-specific roles for ILCs; however, the question of how a small population has large effects on immune homeostasis remains unclear. We identify two mechanisms that ILC3s utilise to exert their effects within intestinal tissue. ILC-driven colitis depends on production of granulocyte macrophage-colony stimulating factor (GM-CSF), which recruits and maintains intestinal inflammatory monocytes. ILCs present in the intestine also enter and exit cryptopatches in a highly dynamic process. During colitis, ILC3s mobilize from cryptopatches, a process that can be inhibited by blocking GM-CSF, and mobilization precedes inflammatory foci elsewhere in the tissue. Together these data identify the IL-23R/GM-CSF axis within ILC3 as a key control point in the accumulation of innate effector cells in the intestine and in the spatio-temporal dynamics of ILCs in the intestinal inflammatory response.
Highlights
Innate lymphoid cells (ILCs) are a recently defined family of evolutionarily ancient cells involved in many facets of host defence
Like IL-17 blockade, treatment with a neutralising anti-IL-22 mAb had no effect on systemic disease or colitis in the proximal colon (Figure 1A&B), indicating that in our facility, IL-22 is redundant for disease induction in this model
The results of this study reveal a new IL-23-driven granulocyte macrophage-colony stimulating factor (GM-CSF) axis that promotes ILC3-mediated acute colitis
Summary
Innate lymphoid cells (ILCs) are a recently defined family of evolutionarily ancient cells involved in many facets of host defence. The ILC3 family includes the prototypic foetal lymphoid tissue inducer (LTi) cells that play a non-redundant role in lymphoid tissue development (Mebius et al, 1997) via lymphotoxin-dependent interactions with stromal cells This pathway is required for lymph node development and for organised lymphoid structures in the gut such as dendritic cell (DC) and ILC containing cryptopatches (CP) (Eberl and Sawa, 2010), B cell, DC and ILC containing isolated lymphoid follicles (ILFs) (Tsuji et al, 2008), and small intestinal Peyer’s Patches (PP) that have a very similar structure to lymph nodes (Cornes, 1965; Mebius et al, 1997). The LTi population can make IL-17 and IL-22 (Cupedo et al, 2009) and contribute to host defence against pathogens, in the gut (Sonnenberg et al, 2011)
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