Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 145

Table 3.37. Precursors of innate lymphoid cells (ILCP) and transcription factors that specify
hematopoietic lineages (Source: [ 272 ]; GATA: DNA sequence GATA-binding transcription factor;
ID2: inhibitor of DNA-binding protein-2, or bHLHb26; NFIL3: interleukin-3-regulated nuclear
factor; NR: nuclear receptor; Tox: thymocyte selection-associated high mobility group box).
Transcription factors and cytokines enable the survival, proliferation, and differentiation of lineage-
specific precursor cells from multipotent progenitors.

Precursor Regulators Generated cell type

+

ID2 ILCP NFIL3, Tox Bone marrow NK precursor (bmNKP)

ID2 + ILCP GATA3 Thymic NK precursor (thyNKP)

ID2 + ILCP ILC2 precursors (ILC2P)

ID2 + ILCP NR1f3-2, Tox LTi precursors (LTiP)

ID2 + ILCP NR1f3-2 ILC17 precursors (ILC17P)

ID2 + ILCP NR1f3-2, bHLHe76 ILC22 precursors (ILC22P)

Lymphoid tissue inducer cells derive from hematopoietic progenitor cells in
the fetal liver [ 273 ]. They seed the developing lymphoid tissue during embryo-
genesis. They initiate the signals that recruit lymphocytes to lymphoid tissue
during development. In adult intestines, LTi-like cells express ROR 2 and lodge

mainly in cryptopatches and isolated lymphoid follicles. LTi-like cells, as well
as cryptopatches and lymph nodes can develop in the intestine in the absence
of gut bacteria. On the other hand, isolated lymphoid follicle LTi-like cells are
created only after gut colonization by bacteria [ 273 ]. Mesenteric LTi-like cells
support the production of antibodies by B cells and prevent intestinal epithelium
damage by bacteria. Like effector helper T H2 cells, mesenteric innate lymphocytes
produce large amounts of interleukin-5, -6, and -13. However, some intestinal innate
lymphocytes do not rely on ROR

γ

2 for development, whereas other types of innate
lymphocytes in the colon express ROR

γ

2. The latter ILC subpopulation secretes
cytokines of the T H2 set as well as interferon-

γ

γ and IL17 and IL22.

3.11.1 Lymphoid Tissue-Inducer Cells

Distinct subpopulations of innate lymphocytes include embryonic lymphoid tissue
inducer cells (LTi) required for fetal lymphoid tissue organogenesis and a population
of natural killer-like cells that operate in gut immune responses, in particular
in intestinal defense before the gut is colonized by intestinal microbiota [ 273 ].
Lymphoid tissue inducer cells and stromal organizer cells are implicated in the
development of lymphoid structures, e.g., lymph nodes and gut-associated lymphoid
tissue that encompasses Peyer's patches, cryptopatches, and multiple isolated
lymphoid follicles.