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Innate lymphoid cells in the skin.

Kim BS - J. Invest. Dermatol. (2014)

Bottom Line: Innate lymphoid cells (ILCs) are part of a heterogeneous family of innate immune cells with newly identified roles in mediating immunity, tissue homeostasis, and pathologic inflammation.Here, we review recent studies delineating the roles of ILCs in the pathogenesis of multiple inflammatory skin disorders and their unique effector functions.Finally, we address how these studies have informed our understanding of the regulation of ILCs and the therapeutic potential of targeting these cells in the context of skin inflammation.

View Article: PubMed Central - PubMed

Affiliation: Division of Dermatology, Department of Medicine, Center for the Study of Itch, Washington University School of Medicine, St. Louis, Missouri, USA.

ABSTRACT
Innate lymphoid cells (ILCs) are part of a heterogeneous family of innate immune cells with newly identified roles in mediating immunity, tissue homeostasis, and pathologic inflammation. Here, we review recent studies delineating the roles of ILCs in the pathogenesis of multiple inflammatory skin disorders and their unique effector functions. Finally, we address how these studies have informed our understanding of the regulation of ILCs and the therapeutic potential of targeting these cells in the context of skin inflammation.

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Related in: MedlinePlus

Regulation and function of human skin ILC responsesHuman skin ILC1s express CD161 and would be predicted to be activated by IL-12 and IL-15 and produce the effector cytokines TNF-α and IFN-γ. Human skin ILC2s express KLRG1, CLA, CCR4, IL-25R (IL-17Rb), IL-33R (ST2), CRTH2 and TSLPR. In response to IL-25, IL-33 and/or TSLP they produce effector cytokines IL-5 and IL-13 and have been implicated in atopic dermatitis. Human skin ILC2s also migrate in response to PGD2. Human skin ILC3s express NKp44 and CLA, produce IL-17 and IL-22 in response to IL-1β and IL-23 and have been implicated in psoriasis.
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Figure 1: Regulation and function of human skin ILC responsesHuman skin ILC1s express CD161 and would be predicted to be activated by IL-12 and IL-15 and produce the effector cytokines TNF-α and IFN-γ. Human skin ILC2s express KLRG1, CLA, CCR4, IL-25R (IL-17Rb), IL-33R (ST2), CRTH2 and TSLPR. In response to IL-25, IL-33 and/or TSLP they produce effector cytokines IL-5 and IL-13 and have been implicated in atopic dermatitis. Human skin ILC2s also migrate in response to PGD2. Human skin ILC3s express NKp44 and CLA, produce IL-17 and IL-22 in response to IL-1β and IL-23 and have been implicated in psoriasis.

Mentions: ILCs are part of a family of innate immune cells that are derived from a common lymphoid progenitor and their development is partially or completely dependent on the common γ-chain (γc or CD132), IL-7, Notch and the transcription factor Inhibitor of DNA binding 2 (Id2) (Mjosberg and Eidsmo, 2014). More recent studies indicate that multiple ILC lineages are also dependent on the transcriptional repressor PLZF, while others (e.g., natural killer cells and lymphoid tissue inducers) are not (Constantinides et al., 2014). Further, all ILC subsets have also been shown to arise from a common lineage-negative (Lin−) Id2+ CD127+ CD25− α4β7+ c-Kit+ precursor (Constantinides et al., 2014; Klose et al., 2014). ILCs are currently categorized into three distinct populations on the basis of their developmental requirements, transcription factor expression profile and/or expression of effector cytokines (Figure 1): group 1 ILCs (ILC1s) are T-bet-dependent IFN-γ- and TNF-α-producing ILCs; RORα-dependent, TCF-1-dependent and GATA3-expressing group 2 ILCs (ILC2s) produce IL-4, IL-5 and IL-13; and RORγt-dependent group 3 ILCs (ILC3s) produce IL-17A and/or IL-22 (Sonnenberg et al., 2013). These ILC groups are analogous to the previously described IFN-γ and TNF-α-producing TH1, IL-4-, IL-5- and IL-13-producing TH2 and IL-17- and IL-22-producing TH17 CD4+ TH cell subsets. However, although ILCs appear to have parallel functions to adaptive CD4+ T cells, they are unique in that they respond to innate signals in the absence of antigen-specificity and have distinct phenotypic and functional profiles.


Innate lymphoid cells in the skin.

Kim BS - J. Invest. Dermatol. (2014)

Regulation and function of human skin ILC responsesHuman skin ILC1s express CD161 and would be predicted to be activated by IL-12 and IL-15 and produce the effector cytokines TNF-α and IFN-γ. Human skin ILC2s express KLRG1, CLA, CCR4, IL-25R (IL-17Rb), IL-33R (ST2), CRTH2 and TSLPR. In response to IL-25, IL-33 and/or TSLP they produce effector cytokines IL-5 and IL-13 and have been implicated in atopic dermatitis. Human skin ILC2s also migrate in response to PGD2. Human skin ILC3s express NKp44 and CLA, produce IL-17 and IL-22 in response to IL-1β and IL-23 and have been implicated in psoriasis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556524&req=5

Figure 1: Regulation and function of human skin ILC responsesHuman skin ILC1s express CD161 and would be predicted to be activated by IL-12 and IL-15 and produce the effector cytokines TNF-α and IFN-γ. Human skin ILC2s express KLRG1, CLA, CCR4, IL-25R (IL-17Rb), IL-33R (ST2), CRTH2 and TSLPR. In response to IL-25, IL-33 and/or TSLP they produce effector cytokines IL-5 and IL-13 and have been implicated in atopic dermatitis. Human skin ILC2s also migrate in response to PGD2. Human skin ILC3s express NKp44 and CLA, produce IL-17 and IL-22 in response to IL-1β and IL-23 and have been implicated in psoriasis.
Mentions: ILCs are part of a family of innate immune cells that are derived from a common lymphoid progenitor and their development is partially or completely dependent on the common γ-chain (γc or CD132), IL-7, Notch and the transcription factor Inhibitor of DNA binding 2 (Id2) (Mjosberg and Eidsmo, 2014). More recent studies indicate that multiple ILC lineages are also dependent on the transcriptional repressor PLZF, while others (e.g., natural killer cells and lymphoid tissue inducers) are not (Constantinides et al., 2014). Further, all ILC subsets have also been shown to arise from a common lineage-negative (Lin−) Id2+ CD127+ CD25− α4β7+ c-Kit+ precursor (Constantinides et al., 2014; Klose et al., 2014). ILCs are currently categorized into three distinct populations on the basis of their developmental requirements, transcription factor expression profile and/or expression of effector cytokines (Figure 1): group 1 ILCs (ILC1s) are T-bet-dependent IFN-γ- and TNF-α-producing ILCs; RORα-dependent, TCF-1-dependent and GATA3-expressing group 2 ILCs (ILC2s) produce IL-4, IL-5 and IL-13; and RORγt-dependent group 3 ILCs (ILC3s) produce IL-17A and/or IL-22 (Sonnenberg et al., 2013). These ILC groups are analogous to the previously described IFN-γ and TNF-α-producing TH1, IL-4-, IL-5- and IL-13-producing TH2 and IL-17- and IL-22-producing TH17 CD4+ TH cell subsets. However, although ILCs appear to have parallel functions to adaptive CD4+ T cells, they are unique in that they respond to innate signals in the absence of antigen-specificity and have distinct phenotypic and functional profiles.

Bottom Line: Innate lymphoid cells (ILCs) are part of a heterogeneous family of innate immune cells with newly identified roles in mediating immunity, tissue homeostasis, and pathologic inflammation.Here, we review recent studies delineating the roles of ILCs in the pathogenesis of multiple inflammatory skin disorders and their unique effector functions.Finally, we address how these studies have informed our understanding of the regulation of ILCs and the therapeutic potential of targeting these cells in the context of skin inflammation.

View Article: PubMed Central - PubMed

Affiliation: Division of Dermatology, Department of Medicine, Center for the Study of Itch, Washington University School of Medicine, St. Louis, Missouri, USA.

ABSTRACT
Innate lymphoid cells (ILCs) are part of a heterogeneous family of innate immune cells with newly identified roles in mediating immunity, tissue homeostasis, and pathologic inflammation. Here, we review recent studies delineating the roles of ILCs in the pathogenesis of multiple inflammatory skin disorders and their unique effector functions. Finally, we address how these studies have informed our understanding of the regulation of ILCs and the therapeutic potential of targeting these cells in the context of skin inflammation.

Show MeSH
Related in: MedlinePlus