Why Innate Lymphoid Cells?

Abstract

Innate lymphoid cells (ILCs) are positioned in tissues perinatally, constitutively express receptors responsive to their organ microenvironments, and perform an arsenal of effector functions that overlap those of adaptive CD4 T cells. Based on knowledge regarding subsets of invariant-like lymphocytes (e.g., natural killer T [NKT] cells, γδ T cells, mucosal-associated invariant T [MAIT] cells, etc.) and fetally derived macrophages, we hypothesize that immune cells established during the perinatal period-including, but not limited to, ILCs-serve intimate roles in tissue that go beyond classical understanding of the immune system in microbial host defense. In this Perspective, we propose mechanisms by which the establishment of ILCs and the tissue lymphoid niche during early development may have consequences much later in life. Although definitive answers require better tools, efforts to achieve deeper understanding of ILC biology across the mammalian lifespan have the potential to lift the veil on the unknown breadth of immune cell functions.

The role of innate lymphoid cells in response to microbes at mucosal surfaces

“…4 ILCs have been reported to participate in the course of several diseases of mucosal tissues, including inflammatory bowel disease, asthma and colorectal cancer; these topics have been reviewed elsewhere. [5][6][7][8] There also have been a number of recent, excellent reviews on ILC biology and function, [9][10][11][12][13] including the role of these cells in general tissue homeostasis. Here we will focus specifically on the role of ILCs in influencing the response to the microbiome during homeostasis and during infection at two mucosal barriers, the lung and the intestine.…”

Immunosenescence is both functional/adaptive and dysfunctional/maladaptive

“…The innate-like T cells comprise the cells displaying a γδTCR, mucosa-associated invariant T (MAIT), iNKT (Invariant Natural Killer T), GEMT (germline-encoded mycolyl lipid-reactive), and innate-like B cells [83]. These cells recognize foreign/self-lipid presented by nonclassical MHC molecules, such as CD1d, MR1, and CD1a [84].…”

Innate lymphocytes—lineage, localization and timing of differentiation

“…M. Kotas and R. Locksley eloquently hypothesized that the initial seeding of ILC populations during gestation may provide instructions to tissues on how to support a tissue-resident immunological niche for organ maintenance later on and that the balance of ILCs established during embryonic development may have important outcomes during challenges in adulthood. 61 These intriguing hypotheses remain untested.…”