Professional Documents
Culture Documents
Jenny Mjsberg
Innate lymphoid cells (ILCs) are recently described microenvironment. However, they can regulate
populations of lymphocytes that lack rearranged tissue homeostasis, inflammation and repair at
antigen-specific receptors. The ILC family has been both mucosal and non-mucosal sites, including the
divided into three main subsets ILC1, ILC2 and intestine, lungs and skin, as well as in adipose and
ILC3 and also includes natural killer (NK) cells lymphoid tissues1. ILC effector functions are mainly
and lymphoid tissue-inducer (LTi) cells. ILCs are mediated through cytokine secretion and through
increasingly appreciated to have important immune direct cellcell interactions with stromal cells and
functions at mucosal surfaces, where they respond other immune cells. This Poster summarizes some of
to signals they receive from other cells in the tissue the key features of ILCs in homeostasis and disease.
Adipose tissue
Intestine Source? Beige
adipocyte Metabolic
homeostasis
Acute IBD Homeostasis and Tumour Helminth infection or IL-25,
infection tissue repair allergen exposure IL-33, IL-13,
Intestinal VIP MetEnk
Mucus Beiging
Intracellular layer Goblet epithelial ILC2
pathogen Stem cell cell cell
regeneration
Epithelial White
fucosylation The role for ILCs in homeostasis and tissue repair adipocyte
Repair Important tissue protective effects of ILC2s and ILC3s have been
Neutrophil Phagocytosis Mucins, IL-25, Mucus described. ILC3s produce IL-22, which is crucial for the repair of
and IL-33 AREG AMPs, IL-33, production
DC Neutrophil IL-9 TSLP
thymic tissue following viral infection14 and for intestinal mucosal
cytotoxicity proliferation
recruitment LT, barrier protection10. In addition, ILC3s can suppress commensal-
iILC1 IFN ILC2 IL-22 specific TH17 cells through IL-2 consumption, preventing intestinal
IL-12, IL-13
ILC2 Fibrosis inflammation15. In the spleen, ILC3s interact with adaptive immune
IL-18 IL-17 IL-22BP
IL-2
cells to maintain memory CD4+ T cells16 and marginal zone (MZ)
ILC1 IL-25 Bcells17. Furthermore, ILC2s in adipose tissue produce met-
ILC1 IL-5 IgE
B cell isotype enkephalin (MetEnk), which promotes beiging of adipose tissue18.
TH2 switch Lung ILC2s contribute to tissue restoration upon viral insult
ILC3 exILC3 ILC3
IFN IL-6, cell
IL-23 IL-1, through the production of AREG19.
MHC
IL-23, Proliferation
IL-12,
IL-18 retinoic
Antigen
TCR
and type 2 Spleen and thymus
M1 IFN acid cytokine
TH17 production Eosinophil Tissue
cell Stromal restoration
Bacterial M1 Eosinophilia after injury
killing cell ICAM1
Inhibition of MSC VCAM1
commensal-specic IL-22,
Tolerogenic TH17 cells through MADCAM1
DC LT LT, Survival
IL-2 consumption 47 Proliferation
IL-23 TNF
integrin IgM, IgA and
CD40L
ILCs contribute to intestinal inflammation and are functionally plastic DC CD40 IgG production
MZ Plasmablast
Human inflammatory bowel disease (IBD) is associated with an increased frequency of IL-17-producing ILC3s20, which parallels findings in mice, in which CD4+
ILC3 B cell dierentiation
T cell DLL1
Helicobacter hepaticus-induced colitis increases the number of IL-17- and IFN-producing ILC3s21. Noteworthy, neutralization of IL-17 in this model, or in
clinical trials, does not ameliorate disease, pointing towards a crucial role for ILC3-derived IFN in IBD. In mice, intestinal environmental cues induce CD30L APRIL
T-bet expression in RORt+NCR+ ILC3s, which is crucial for defence against Salmonella infection22. However, this causes collateral damage that presents T cell memory CD30 OX40L BAFF
maintenance OX40
as enterocolitis. Paralleling these observations, human Crohn's disease is associated with an accumulation of IFN-producing ILC1s23. ILC1s can be
derived from ILC3s under the influence of IL-12, whereas IL-23 and retinoic acid exposure lead to ILC3 re-differentiation24. Hence, a finely tuned balance CD4+ Neutrophil
T cell GM-CSF
of ILC1s and ILC3s ensures tissue integrity while maintaining immune defence in the intestine.