Traditionally, immunologists have classified immune responses into two types: innate and adaptive. However, natural killer (NK) cells, lymphoid-tissue inducer (LTi) cells and the recently identified subsets of innate lymphoid cells (ILCs) do not fit into this scheme. ILCs lack a recombined antigen receptor and are poised to produce interferon-γ or T helper 2 (TH2) and TH17 cell-associated cytokines following stimulation. Moreover, studies on other innate-like lymphocytes, including γδ T cells, NKT cells, B1 cells and marginal zone B cells, suggest that there are no clear boundaries between innate and adaptive immunity.
The Review and Perspective articles in this Focus issue describe the phenotypes and functions of innate-like lymphocytes, and how these may challenge the current dogmas in immunology. In addition, a Guidelines article proposes a unifying nomenclature for all ILC subsets that will hopefully help to prevent confusion in this rapidly evolving field.
Foreword
Shades of grey — the blurring view of innate and adaptive immunity
p73 | doi:10.1038/nri3389
Research Highlights
Innate-like lymphocytes: Will the real ILC1 please stand up?
doi:10.1038/nri3397
Nature Reviews Immunology, 13, 67 (2013)
T-bet instructs the development of IFNγ-producing innate lymphoid cells in mice and humans.
In brief
Innate-like lymphocytes: An antifungal role for innate lymphoid cells | PDF (92 KB)
p71 | doi:10.1038/nri3394
Nature Reviews Immunology, 13, 71 (2013)
Innate-like lymphocytes: Diet shapes the natural killer cell response | PDF (92 KB)
p71 | doi:10.1038/nri3395
Nature Reviews Immunology, 13, 71 (2013)
Reviews
Innate lymphoid cells — how did we miss them?
Jennifer A. Walker, Jillian L. Barlow & Andrew N. J. McKenzie
p75 | doi:10.1038/nri3349
This Review discusses the key features of innate lymphoid cells (ILCs), which despite their fairly recent identification have emerged as an important cellular component of the immune system. ILCs can rapidly release effector cytokines and promote protective immunity following infection. However, aberrant activation of ILCs may contribute to immunopathology in allergic and autoimmune diseases.
Six-of-the-best: unique contributions of γδ T cells to immunology
Pierre Vantourout & Adrian Hayday
p88 | doi:10.1038/nri3384
This Review critically assesses six signatory roles of the often overlooked γδ T cells that may collectively distinguish these cells from αβ T cells, and thereby define their unique contributions to lymphocyte biology.
Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions
Patrick J. Brennan, Manfred Brigl & Michael B. Brenner
p101 | doi:10.1038/nri3369
Invariant natural killer T (iNKT) cells are innate-like lymphocytes that express T cell receptors that can be activated by lipid antigens presented on CD1d molecules. Here, the authors describe different models of iNKT cell activation and discuss how activated iNKT cells can contribute to both protective and pathological immune responses.
Marginal zone B cells: virtues of innate-like antibody-producing lymphocytes
Andrea Cerutti, Montserrat Cols & Irene Puga
p118 | doi:10.1038/nri3383
Marginal zone B cells are strategically positioned at the interface between the circulation and the white pulp of the spleen, where they can mediate a rapid, innate-like humoral response against both pathogens and commensals that breach the mucosal barrier. Understanding the interplay of these cells with other immune components and the species-specific differences between mice and humans is of clinical importance.
Perspectives
Variable NK cell receptors and their MHC class I ligands in immunity, reproduction and human evolution
Peter Parham & Ashley Moffett
p133 | doi:10.1038/nri3370
The role of natural killer (NK) cells in both immunity to infection and reproductive success is postulated to have placed competing demands on the evolution of NK cell receptors and their MHC class I ligands during the migration of humans out of Africa.
Innate lymphoid cells — a proposal for uniform nomenclature
Hergen Spits, David Artis, Marco Colonna, Andreas Diefenbach, James P. Di Santo, Gerard Eberl, Shigeo Koyasu, Richard M. Locksley, Andrew N. J. McKenzie, Reina E. Mebius, Fiona Powrie & Eric Vivier
p145 | doi:10.1038/nri3365
Innate lymphoid cells (ILCs) have key roles in immune responses, lymphoid tissue development and tissue regeneration. Recently, several new ILC subsets were identified. Here, the authors propose the use of a uniform nomenclature to describe all ILC subsets to avoid confusion and further promote the development of this field.
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