Limits...
Innate lymphoid cells, possible interaction with microbiota.

Moro K, Koyasu S - Semin Immunopathol (2014)

Bottom Line: ILCs are present in a wide variety of epithelial compartments and occupy an intermediate position between acquired immune cells and myeloid cells.ILCs are now classified into three groups: group 1 ILC, group 2 ILC, and group 3 ILC based on their cytokine production patterns that correspond to the helper T cell subsets Th1, Th2, and Th17, respectively.ILCs play important roles in protection against various invading microbes including multicellular parasites, and in the maintenance of homeostasis and repair of epithelial layers.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Immune Cell Systems, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, , Tsurumi-ku, , Yokohama, 230-0045, Japan, kazuyo.moro@riken.jp.

ABSTRACT
Recent studies have identified novel lymphocyte subsets named innate lymphoid cells (ILCs) lacking antigen-specific receptors. ILCs are present in a wide variety of epithelial compartments and occupy an intermediate position between acquired immune cells and myeloid cells. ILCs are now classified into three groups: group 1 ILC, group 2 ILC, and group 3 ILC based on their cytokine production patterns that correspond to the helper T cell subsets Th1, Th2, and Th17, respectively. ILCs play important roles in protection against various invading microbes including multicellular parasites, and in the maintenance of homeostasis and repair of epithelial layers. Excessive activation of ILCs, however, leads to various inflammatory disease conditions. ILCs have thus attracted interests of many researchers in the fields of infectious immunity, inflammatory diseases, and allergic diseases. Because epithelial cells sense alterations in environmental cues, it is important to understand the functional interaction between epithelial cells, ILCs, and environmental factors such as commensal microbiota. We discuss in this review developmental pathways of ILCs, their functions, and contribution of commensal microbiota to the differentiation and function of ILCs.

Show MeSH

Related in: MedlinePlus

Developmental pathways of ILCs. All ILCs require Id2 signaling for their development. cNK cells branch out earlier than other helper-like ILCs and LTi cells branch out from CHILP. Cell fate determination processes of ILC, ILC2s, and ILC3s from PLZF+ ILCP are still unknown, but there are two possibilities: a determined after PLZF+ ILCP or b cell fate determinations are already established before or at the PLZF+ ILCP stage
© Copyright Policy - OpenAccess
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4281376&req=5

Fig1: Developmental pathways of ILCs. All ILCs require Id2 signaling for their development. cNK cells branch out earlier than other helper-like ILCs and LTi cells branch out from CHILP. Cell fate determination processes of ILC, ILC2s, and ILC3s from PLZF+ ILCP are still unknown, but there are two possibilities: a determined after PLZF+ ILCP or b cell fate determinations are already established before or at the PLZF+ ILCP stage

Mentions: All lymphocytes are derived from common lymphoid progenitors (CLP) in the fetal liver and adult bone marrow and are characterized by the lineage (Lin)−c-KitintSca-1+IL-7Rα+ phenotype. Knockout studies have identified the transcription factor Id2 and cytokine signals mediated by γc as essential factors for the development of all ILCs. T and B cells develop independent of Id2 but require Rag1 and Rag2 genes for recombination of their antigen receptors. On the other hand, Rag1 and Rag2 genes are dispensable for differentiation of ILCs. Interestingly, Yang et al. showed by fate mapping analysis that a fraction of ILC2s once expressed Rag2, demonstrating the close relationship between antigen receptor-expressing lymphocytes and ILCs [3]. It was later shown that Gata3 is critical for the differentiation of ILC1, ILC2s, ILC3s, and LTi but not for cNK cells. Klose et al. recently reported the existence of a Lin−Id2+IL-7Rα+CD25−α4β7+Flt3− progenitor population that they named common helper-like innate lymphoid cell progenitor (CHILP) capable of developing into all ILC subsets except cytotoxic cNK cells, indicating that cNK cells are distinct from other ILCs [4]. E4BP4 or NF-IL3 was originally reported as an essential transcription factor for cNK cell differentiation, but it was later shown that the lack of E4BP4 impairs the differentiation of all ILCs by the reduction of CHILP, indicating that E4BP4 also controls the differentiation of all ILCs, not only that of cNK cells. In addition, Constantinides et al. found that PLZF, which has been known to control differentiation of innate-type CD1d-restricted NKT cells [5, 6], is transiently expressed in CHILP during ILC differentiation. Fate mapping studies for the expression of Zbtb16, the gene encoding PLZF, showed labeling of ILC1, ILC2s, and ILC3s but not cNK cells and LTi cells [7]. Consistent with this observation, Zbtb16-deficient mice showed normal development of cNK cells and LTi cells whereas differentiation of ILC1, ILC2s, and ILC3s were variously affected. Accordingly, PLZF+ CHILP differentiates to ILC1, ILC2s, and ILC3s but not to cNK cells or LTi cells based on adoptive transfer experiments and clonal differentiation assays [7]. These recent results collectively showed that cNK cells branch out from CLP prior to differentiation of CLP to CHILP, followed by branching out of LTi before acquisition of PLZF expression by CHILP. Lineage specification of ILC1, ILC2s, and ILC3s from PLZF+ CHILP takes place by acquisition of T-bet, Gata3, and RORγt expression, respectively (Fig. 1a).Fig. 1


Innate lymphoid cells, possible interaction with microbiota.

Moro K, Koyasu S - Semin Immunopathol (2014)

Developmental pathways of ILCs. All ILCs require Id2 signaling for their development. cNK cells branch out earlier than other helper-like ILCs and LTi cells branch out from CHILP. Cell fate determination processes of ILC, ILC2s, and ILC3s from PLZF+ ILCP are still unknown, but there are two possibilities: a determined after PLZF+ ILCP or b cell fate determinations are already established before or at the PLZF+ ILCP stage
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4281376&req=5

Fig1: Developmental pathways of ILCs. All ILCs require Id2 signaling for their development. cNK cells branch out earlier than other helper-like ILCs and LTi cells branch out from CHILP. Cell fate determination processes of ILC, ILC2s, and ILC3s from PLZF+ ILCP are still unknown, but there are two possibilities: a determined after PLZF+ ILCP or b cell fate determinations are already established before or at the PLZF+ ILCP stage
Mentions: All lymphocytes are derived from common lymphoid progenitors (CLP) in the fetal liver and adult bone marrow and are characterized by the lineage (Lin)−c-KitintSca-1+IL-7Rα+ phenotype. Knockout studies have identified the transcription factor Id2 and cytokine signals mediated by γc as essential factors for the development of all ILCs. T and B cells develop independent of Id2 but require Rag1 and Rag2 genes for recombination of their antigen receptors. On the other hand, Rag1 and Rag2 genes are dispensable for differentiation of ILCs. Interestingly, Yang et al. showed by fate mapping analysis that a fraction of ILC2s once expressed Rag2, demonstrating the close relationship between antigen receptor-expressing lymphocytes and ILCs [3]. It was later shown that Gata3 is critical for the differentiation of ILC1, ILC2s, ILC3s, and LTi but not for cNK cells. Klose et al. recently reported the existence of a Lin−Id2+IL-7Rα+CD25−α4β7+Flt3− progenitor population that they named common helper-like innate lymphoid cell progenitor (CHILP) capable of developing into all ILC subsets except cytotoxic cNK cells, indicating that cNK cells are distinct from other ILCs [4]. E4BP4 or NF-IL3 was originally reported as an essential transcription factor for cNK cell differentiation, but it was later shown that the lack of E4BP4 impairs the differentiation of all ILCs by the reduction of CHILP, indicating that E4BP4 also controls the differentiation of all ILCs, not only that of cNK cells. In addition, Constantinides et al. found that PLZF, which has been known to control differentiation of innate-type CD1d-restricted NKT cells [5, 6], is transiently expressed in CHILP during ILC differentiation. Fate mapping studies for the expression of Zbtb16, the gene encoding PLZF, showed labeling of ILC1, ILC2s, and ILC3s but not cNK cells and LTi cells [7]. Consistent with this observation, Zbtb16-deficient mice showed normal development of cNK cells and LTi cells whereas differentiation of ILC1, ILC2s, and ILC3s were variously affected. Accordingly, PLZF+ CHILP differentiates to ILC1, ILC2s, and ILC3s but not to cNK cells or LTi cells based on adoptive transfer experiments and clonal differentiation assays [7]. These recent results collectively showed that cNK cells branch out from CLP prior to differentiation of CLP to CHILP, followed by branching out of LTi before acquisition of PLZF expression by CHILP. Lineage specification of ILC1, ILC2s, and ILC3s from PLZF+ CHILP takes place by acquisition of T-bet, Gata3, and RORγt expression, respectively (Fig. 1a).Fig. 1

Bottom Line: ILCs are present in a wide variety of epithelial compartments and occupy an intermediate position between acquired immune cells and myeloid cells.ILCs are now classified into three groups: group 1 ILC, group 2 ILC, and group 3 ILC based on their cytokine production patterns that correspond to the helper T cell subsets Th1, Th2, and Th17, respectively.ILCs play important roles in protection against various invading microbes including multicellular parasites, and in the maintenance of homeostasis and repair of epithelial layers.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Immune Cell Systems, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, , Tsurumi-ku, , Yokohama, 230-0045, Japan, kazuyo.moro@riken.jp.

ABSTRACT
Recent studies have identified novel lymphocyte subsets named innate lymphoid cells (ILCs) lacking antigen-specific receptors. ILCs are present in a wide variety of epithelial compartments and occupy an intermediate position between acquired immune cells and myeloid cells. ILCs are now classified into three groups: group 1 ILC, group 2 ILC, and group 3 ILC based on their cytokine production patterns that correspond to the helper T cell subsets Th1, Th2, and Th17, respectively. ILCs play important roles in protection against various invading microbes including multicellular parasites, and in the maintenance of homeostasis and repair of epithelial layers. Excessive activation of ILCs, however, leads to various inflammatory disease conditions. ILCs have thus attracted interests of many researchers in the fields of infectious immunity, inflammatory diseases, and allergic diseases. Because epithelial cells sense alterations in environmental cues, it is important to understand the functional interaction between epithelial cells, ILCs, and environmental factors such as commensal microbiota. We discuss in this review developmental pathways of ILCs, their functions, and contribution of commensal microbiota to the differentiation and function of ILCs.

Show MeSH
Related in: MedlinePlus