Innate Lymphoid Cell (ILC) Lineage Pathway and … Innate Lymphoid Cell (ILC) Lineage Pathway and...

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Page 1: Innate Lymphoid Cell (ILC) Lineage Pathway and … Innate Lymphoid Cell (ILC) Lineage Pathway and Localization Adipose issue o esentery Cross section o mall Intestine IL IL ETS-1 PU.1

RnDSy-lu-2945

Innate Lymphoid Cell (ILC) Lineage Pathway and Localization

Adipose Tissue of Mesentery

Cross section of Small Intestine

IL-2IL-12

ETS-1PU.1

IL-15

IL-7

GATA-3

Ikaros

IL-12IL-18

PerforinGranzyme

CD56dim

CD16+

CD117/c-kit– IFN-γTNF-αIL-10IL-13

IL-4IL-5IL-9IL-13Amphiregulin

IL-25IL-33TSLP

CD25/IL-2 Rα+

CD45+

CD90/Thy1+

CD117/c-kit+

CD127/IL-7 Rα+

CD161/NKRP1A+

IL-17 RB+

ST2/IL-33 R+

TSLP R+

CRTH-2+

ICOS+

Sca-1+

KLRG1+

GATA-3high

IL-7

RORαGATA-3

ID2Notch

IL-7

IL-7

IFN-γ

IL-2IL-12

IL-17IL-22IFN-γ

IL-23IL-1β

IL-17IL-22LTα/β

CD4+

CD7+

CD90/Thy1+

CD117/c-kithigh

CD127/IL-7 Rα+

CD161/NKRP1A+

CXCR5+

CXCR6+

CCR6+

IL-1 RI+

IL-2 Rα+

IL-23 R+

RORγthigh

RORγtAHRRUNX1

RORγtAhRT-bet

IL-23IL-1β

IL-2IL-23

NKp44–

NKp46–

CD25/IL-2 Rα+

CD56+

CD90/Thy1+

CD117/c-kithigh

CD127/IL-7 Rα+

Sca-1+

IL-1R+

IL-12 Rβ1+

IL-23 R+

CCR6–

T-betlow

RORγthigh

NKp44+

NKp46+

CD25/IL-2 Rαlow

CD44+

CD56+

CD90/Thy1+

CD117/c-kitlow

CD127/IL-7 Rαlow

CD161/NKRP1A+

IL-12 Rβ1high

Sca-1+

IL-1 R+

IL-2 Rβ+

IL-23 R+

CCR6–

T-bethigh

RORγtlow

IFN-γIL-22

T-bethigh

T-bethigh

T-betlow

T-betlow

CD127/IL-7 Rα+

Integrin α4β7+

ID2+

PLZF–

T-betEOMESNFIL3/E4BP4

IL-12IL-15

IFN-γPerforinGranzyme

IFN-γ

T-bet

Integrin α4β7+

CD25/IL-2 Rα–

CD27+

C1q R1/CD93–

CD117/c-kit+

2B4/CD244+

CD127/IL-7 Rα+

Sca-1+

IL-2 Rβ–

PLZFhigh

NKp44–

CD16–

CD34–

CD56–

CD69–/+

CD94–

CD117/c-kit–

CD127/IL-7 Rα+

CD161/NKRP1A+

CXCR3+

CCL3+

IL-1 R+

IL-12 Rβ2+

IL-15 Rα–

ICOS+

T-bet+

NKp44+

NKp46+

CD9+

CD56+

CD39+

CD69+

CD101/IGSF2+

CD103/Integrin αE+ (human)IL-2 Rβ+

CD127/IL-7 Rα+ (human)CD160+ (mouse)CD161/NKRP1A+

Integrin α4β7+

CXCR6+

IL-12 Rβ1+

IL-12 Rβ2+

IL-15 Rα+

T-bet+

IL-12IL-18

NKp44–

CD25/IL-2 Rα+

CD56–

CD117/c-kit–

CD127/IL-7 Rα+

IL-2 Rβ+

T-bethigh

RORγtlow

CD56bright

CD16dim/–

CD117/c-kit+

T-betNFIL3/E4BP4

Mesentery ofSmall Intestine

NKP

CLP

CLP

iILC2iNK

mNK

Cytotoxic NK cell

ImmunoregulatoryNK cell

ILC2

IntraepithelialILC1 ILC1

ILC1

ILCP

LTiP LTi

NCR+

ILC3

NCR–

ILC3

CD7high

CD8+

CD34+

IL-2 Rβ+

CD161/NKRP1A+

CD7high

CD34–

CD56+

CD117/c-kitlow

CD127/IL-7 Rα–

CD161/NKRP1A+

IL-2 Rβ+NKp46+

Integrin αM/CD11b+

Fcγ RIII/CD16+

CD25/IL-2 Rα+

CD56+

CD90/Thy1+

CD127/IL-7 Rα+

CD161/NKRP1A+

NKG2D/CD314+

KIR/CD158+

IL-2 Rβ+

IL-12 Rβ2+

Tunica Muscularis

Tunica Submucosa

Muscularis Mucosa

Intestinal Lamina Propria

Intestinal Epithelium

Intraepithelial ILC1

Dendritic Cell

Intestinal Villi

ILC1

Natural Killer cell (NK)

Macrophage

Peyer’s Patch

NCR+/–ILC3

Group 1NKP, iNK, mNK, Cytotoxic NK cell, Immunoregulatory NK cell, ILC1, Intraepithelial ILC1

Group 2iILC2, ILC2

Group 3LTiP, LTi, NCR+ILC3, NCR–ILC3

Lymphoid Tissue inducer cell (LTi)

ILC Groups

Fat-associatedlymphoid cluster

ILC2 Localization

KeyCLP: Common Lymphoid ProgenitorNKP: NK Cell PrecursoriNK: immature NK cellmNK: mature NK cellILCP: Innate Lymphoid Cell ProgenitorLTiP: Lymphoid Tissue inducer ProgenitorLTi: Lymphoid Tissue inducer cellNCR: Natural Cytotoxicity Triggering ReceptoriILC2: immature ILC2

Transcription factors are indicated in bold font.

NOTE: This poster conveys a general overview and should be considered neither comprehensive nor definitive. The details of this information are understood to be subject to interpretation. © R&D Systems 2016

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Learn more | rndsystems.com/ilcidentification

Innate lymphoid cells (ILCs) are important effectors and regulators involved in immune surveillance and the preservation of tissue integrity. Consistent with the suggestion that ILCs are involved in the early detection of pathogens, ILCs are present at mucosal surfaces and respond to molecules secreted from the epithelium. They are derived from a common lymphoid progenitor cell (CLP) that originates from fetal liver or adult bone marrow. Sequentially expressed transcription factors orchestrate the differentiation of the CLP into either an LTi progenitor cell (LTiP), an NK progenitor cell (NKP), or an ILC progenitor (ILCP). Because ILCs share developmental and functional similarities with helper T (Th) cells, a nomenclature for ILCs has been established based on Th cell classification.

ILCs are categorized into three groups according to the transcription factors mediating their development and the cytokines they secrete. Predominantly localized in the intestinal lamina propria (LTi cells, NCR-ILC3, NK cells and ILC1) and epithelium (Intraepithelial ILC1), group 1 and group 3 ILCs mediate the balance between symbiotic microbiota and the intestinal immune system and are implicated in the response against pathogenic gut bacteria. Group 2 ILCs have been described as part of fat-associated lymphoid clusters in human and mouse mesentery, and are normally present in human and mouse airway mucosa and skin.