Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 144

Table 3.36. Categories of innate lymphoid cells (ILC; Source: [ 272 ]). The ILC1 subset includes
CD56 high ,CD16 natural killer (NK) cells. The ILC2 subset comprises natural helper (NH) cells,

or nuocytes. The ILC17 and ILC22 subsets encompass IL17-producing lymphoid tissue-inducer
(LTi) cells and NKR

−

+ LTi-like (NK22 or NCR22) cells, respectively.

Subset Regulators Function and targets

Plasmalemmal and released agents

Thymic NK (ILC1) IL7/15 Intracellular pathogens, inflammation

Ifn

γ

Conventional NK IL15 Intracellular pathogens, inflammation

CD16 − Ifn γ

CD16 high

Ifn γ

Nuocyte (ILC2, NH) common Extracellular parasites, allergy

γ chain IL13

IL25/33

NR1f3-2 + LTi IL7 Formation of lymph nodes and

TNFSF11 isolated lymphoid follicles

TNFSF2-TNFSF3 trimer, TNFSF1

+

NR1f3-2 ILC17 IL7 Extracellular bacteria

IL23 IL17

NR1f3-2 + ILC22 IL7 Extracellular bacteria

IL1 β IL22

The functional differentiation of ILC subsets is controlled by certain transcription
factors. Their formation needs the transcriptional repressor inhibitor of DNA
binding ID2 (or bHLHb26) and signaling via the common IL2R chain [ 272 ].

Whereas the development of B and T cells and dendritic cells requires members
of the E2A family (bHLHb21 E12 , bHLHb21 E47 , bHLHb19, and bHLHb20), E2A
family proteins preclude the development of several ILC subsets This inhibition
is overcome by inhibitors of DNA binding that heterodimerize with E2A proteins,
thereby inactivating these transcription factors. Conversely, in human hematopoietic
precursor cells, ID proteins promote the development of ILC cells, but impede the
development of B and T cells and plasmacytoid dendritic cells.
Innate lymphoid cells constitute subpopulations of immunocytes that synthesize
cytokines also expressed by helper T cells, but lack markers of mature lymphoid
cells such as T-cell antigen receptors. Like some helper T-cell lineages, a proportion
of innate lymphocytes express the transcription factor retinoic acid receptor-related
orphan receptor ROR

γ

2 (or NR1f3-2).
Innate lymphocytes may be generated by SCA1

γ

+
progenitors that produce the transcriptional regulator inhibitor of DNA-binding
protein ID2 [ 273 ]. Topographical and functional compartmentation of NR1f3-2

+ ,PTPRc + ,IL7R γ+ ,SCFR

+

ILCs depends on CCR6 chemokine receptor that is targeted by CCL20 and β -

defensins produced by epithelial cells [ 274 ].