Editors' ChoiceImmunology

New connections: Regulating innate lymphoid cells

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Sci. Signal.  03 May 2016:
Vol. 9, Issue 426, pp. ec105
DOI: 10.1126/scisignal.aag0164

Innate lymphoid cells (ILCs) are immune cells that are classified according to the types of cytokines that they produce, with different subsets performing distinct functions. By rapidly producing cytokines at mucosal surfaces, such as in the gut, ILCs protect barriers and regulate that balance between inflammatory responses to pathogenic bacteria and tolerance of commensal organisms. In Science, Gomez de Agüero et al. found that colonizing pregnant female mice with bacteria shaped the immune system of the pups by increasing their number of group 3 ILCs (ILC3s). Thus, the offspring of the colonized pregnant mice were more likely than control pups to avoid inflammation in response to microbial products. Also in Science, Duffin et al. showed a role for prostaglandin E2 (PGE2) in dampening systemic inflammation. Mice with impaired PGE2 production had increased systemic inflammation due to the leakage of bacteria from the gut. PGE2 was required to stimulate ILC3s to produce the cytokine IL-22, and this signaling pathway was required to prevent gut barrier dysfunction and translocation of bacteria. The types of immune responses mediated by ILC3s depend on the relative numbers of subsets that are classified by the presence or absence of the cell surface receptor NCR. A pair of papers in Science Signaling revealed the mechanisms underlying the differentiation and plasticity of these subsets. Chea et al. found that signaling by Notch2 was required for the differentiation of most NCR ILC3s into NCR+ ILC3s, whereas Viant et al. showed that the cytokine transforming growth factor–β (TGF-β) drove differentiation in the opposite direction. Thus, the relative distributions of Notch ligands and TGF-β in tissues would determine the proportions of ILC3 subsets available, findings with implications for inflammation and tolerance.

M. Gomez de Agüero, S. C. Ganal-Vonarburg, T. Fuhrer, S. Rupp, Y. Uchimura, H. Li, A. Steinert, M. Heikenwalder, S. Hapfelmeier, U. Sauer, K. D. McCoy, A. J. Macpherson, The maternal microbiota drives early postnatal innate immune development. Science 351, 1296–1302 (2016). [Abstract]

R. Duffin, R. A. O’Connor, S. Crittenden, T. Forster, C. Yu, X. Zheng, D. Smyth, C. T. Robb, F. Rossi, C. Skouras, S. Tang, J. Richards, A. Pellicoro, R. B. Weller, R. M. Breyer, D. J. Mole, J. P. Iredale, S. M. Anderton, S. Narumiya, R. M. Maizels, P. Ghazal, S. E. Howie, A. G. Rossi, C. Yao, Prostaglandin E2 constrains systemic inflammation through an innate lymphoid cell–IL-22 axis. Science 351, 1333–1338 (2016). [Abstract]

S. Chea, T. Perchet, M. Petit, T. Verrier, D. Guy-Grand, E.-G. Banchi, C. A. J. Vosshenrich, J. P. Di Santo, A. Cumano, R. Golub, Notch signaling in group 3 innate lymphoid cells modulates their plasticity. Sci. Signal. 9, ra45 (2016). [Abstract]

C. Viant, L. C. Rankin, M. J. H. Girard-Madoux, C. Seillet, W. Shi, M. J. Smyth, L. Bartholin, T. Walzer, N. D. Huntington, E. Vivier, G. T. Belz, Transforming growth factor–β and Notch ligands act as opposing environmental cues in regulating the plasticity of type 3 innate lymphoid cells. Sci. Signal. 9, ra46 (2016). [Abstract]

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