Resident Skin-specific γδ T Cells Provide Local, Nonredundant Regulation of Cutaneous Inflammation

The function of the intraepithelial lymphocyte (IEL) network of T cell receptor (TCR) γδ+ (Vγ5+) dendritic epidermal T cells (DETC) was evaluated by examining several mouse strains genetically deficient in γδ T cells (δ−/− mice), and in δ−/− mice reconstituted with DETC or with different γδ cell subpopulations. NOD.δ−/− and FVB.δ−/− mice spontaneously developed localized, chronic dermatitis, whereas interestingly, the commonly used C57BL/6.δ−/− strain did not. Genetic analyses indicated a single autosomal recessive gene controlled the dermatitis susceptibility of NOD.δ−/− mice. Furthermore, allergic and irritant contact dermatitis reactions were exaggerated in FVB.δ−/−, but not in C57BL/6.δ−/− mice. Neither spontaneous nor augmented irritant dermatitis was observed in FVB.β−/− δ−/− mice lacking all T cells, indicating that αβ T cell–mediated inflammation is the target for γδ-mediated down-regulation. Reconstitution studies demonstrated that both spontaneous and augmented irritant dermatitis in FVB.δ−/− mice were down-regulated by Vγ5+ DETC, but not by epidermal T cells expressing other γδ TCRs. This study demonstrates that functional impairment at an epithelial interface can be specifically attributed to absence of the local TCR-γδ+ IEL subset and suggests that systemic inflammatory reactions may more generally be subject to substantial regulation by local IELs.

• Publication year

  2002

• Venue

  Journal of Experimental Medicine

• Publication date

  2002-04-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1084/jem.20012000PMID 11927630PMCID 2193718
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• The absence of all T cells in FVB.β−/− δ−/− mice showed that αβ T cell-mediated inflammation is the target of γδ-mediated down-regulation.

  Confidence 0.95

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewjihoonc (k5vuy3tzcm) review
• Vγ5+ DETC reconstitution down-regulated both spontaneous and augmented irritant dermatitis in FVB.δ−/− mice, whereas epidermal T cells expressing other γδ TCRs did not.

  Confidence 0.99

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewjihoonc (k5vuy3tzcm) review
• Allergic and irritant contact dermatitis responses were exaggerated in FVB.δ−/− mice but not in C57BL/6.δ−/− mice.

  Confidence 0.97

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewjihoonc (k5vuy3tzcm) review
• NOD.δ−/− and FVB.δ−/− mice spontaneously developed localized, chronic dermatitis, whereas C57BL/6.δ−/− mice did not.

  Confidence 0.98

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewjihoonc (k5vuy3tzcm) review

• allergic and irritant contact dermatitis reactions

  phenotype, immune response

  Skin inflammatory responses induced by allergen exposure or chemical irritation and scored in the mouse dermatitis tests.

  Aliases: contact dermatitis reactions, allergic dermatitis and irritant dermatitis

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewjihoonc (k5vuy3tzcm) review
• c57bl/6.δ−/− mice

  animal model, mouse strain

  C57BL/6 background mice genetically deficient in γδ T cells and used as a comparison strain in the dermatitis assays.

  Aliases: C57BL/6.delta knockout mice, C57BL/6 gamma-delta-deficient mice

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewjihoonc (k5vuy3tzcm) review
• epidermal t cells expressing other γδ tcrs

  cell type, T cell subset

  Epidermal γδ T cells bearing T-cell receptors other than Vγ5, used as an alternative reconstitution population.

  Aliases: other γδ epidermal T cells, non-Vγ5 γδ epidermal T cells

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewjihoonc (k5vuy3tzcm) review
• fvb.β−/− δ−/− mice

  animal model, mouse strain

  FVB background mice lacking both β-chain and δ-chain T-cell receptors, leaving them without conventional αβ or γδ T cells.

  Aliases: FVB beta and delta double knockout mice, FVB.β knockout δ knockout mice

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewjihoonc (k5vuy3tzcm) review
• fvb.δ−/− mice

  animal model, mouse strain

  FVB background mice genetically deficient in γδ T cells and used for dermatitis and reconstitution experiments.

  Aliases: FVB.delta knockout mice, FVB gamma-delta-deficient mice

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewjihoonc (k5vuy3tzcm) review
• localized, chronic dermatitis

  condition, phenotype

  Persistent skin inflammation confined to specific local sites on the mouse skin.

  Aliases: chronic localized dermatitis, localized chronic dermatitis

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewjihoonc (k5vuy3tzcm) review
• nod.δ−/− mice

  animal model, mouse strain

  NOD background mice genetically deficient in γδ T cells and used to examine susceptibility to skin inflammation.

  Aliases: NOD.delta knockout mice, NOD gamma-delta-deficient mice

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewjihoonc (k5vuy3tzcm) review
• vγ5+ detc

  cell type, T cell subset

  Resident dendritic epidermal T cells that express the Vγ5 T-cell receptor and populate the epidermis.

  Aliases: Vγ5 positive dendritic epidermal T cells, Vγ5+ dendritic epidermal T cells, DETC

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewjihoonc (k5vuy3tzcm) review
• αβ t cell-mediated inflammation

  immune response, phenotype

  Inflammatory responses driven by conventional alpha-beta T cells in the skin.

  Aliases: alpha beta T cell-mediated inflammation, αβ-mediated inflammation

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewjihoonc (k5vuy3tzcm) review

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