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Literature DB >> 31118160

Keratinocyte-derived TGFβ is not required to maintain skin immune homeostasis.

Yi Yang¹, Yukari Zenke², Toshiro Hirai³, Daniel H Kaplan⁴.

Abstract

BACKGROUND: Transforming growth factor beta 1 (TGFβ) is known to be a regulator of autoimmunity. Loss of TGFβ leads to severe multi-organ autoimmunity in mice. In skin, role of TGFβ in suppressing autoimmunity is unclear.
OBJECTIVE: Determine whether Keratinocyte (KC)-derived TGFβ is required for skin immune homeostasis.
METHODS: We generated K14-CreERT2TGFβ1fl/fl (TGFβΔKC) mice allowing for tamoxifen-induced deletion of TGFβ1 in KC. The phenotype of skin was analyzed and compared to mice in which epidermal activation of TGFβ is impaired.
RESULTS: KC was the major source of TGFβ in epidermis. Topical tamoxifen application led to efficient TGFβ1 deletion. The expected acanthosis was observed but no inflammatory infiltrate or altered numbers of resident immune cells were evident. Similarly, Itgb6-/-x K14Cre Itgb8f/f (Itgb6-/-Itgb8ΔKC) mice lacking both epidermal TGFβ-activating integrins showed no evidence of cutaneous inflammation.
CONCLUSIONS: KC-derived TGFβ and epidermal TGFβ activation are not required to suppress skin autoimmunity in steady state.

Entities: CellLine Chemical Disease Gene Species

Keywords: Keratinocyte; Skin; TGFβ; α(v)β(6); α(v)β(8)

Mesh：

Substances：

Year: 2019 PMID： 31118160 PMCID： PMC6602918 DOI： 10.1016/j.jdermsci.2019.04.008

Source DB: PubMed Journal: J Dermatol Sci ISSN： 0923-1811 Impact factor: 4.563

36 in total

1. Control of murine hair follicle regression (catagen) by TGF-beta1 in vivo.

Authors: K Foitzik; G Lindner; S Mueller-Roever; M Maurer; N Botchkareva; V Botchkarev; B Handjiski; M Metz; T Hibino; T Soma; G P Dotto; R Paus
Journal: FASEB J Date: 2000-04 Impact factor: 5.191

2. Epidermal langerhans cell-deficient mice develop enhanced contact hypersensitivity.

Authors: Daniel H Kaplan; Mathew C Jenison; Sem Saeland; Warren D Shlomchik; Mark J Shlomchik
Journal: Immunity Date: 2005-12 Impact factor: 31.745

3. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis.

Authors: J S Munger; X Huang; H Kawakatsu; M J Griffiths; S L Dalton; J Wu; J F Pittet; N Kaminski; C Garat; M A Matthay; D B Rifkin; D Sheppard
Journal: Cell Date: 1999-02-05 Impact factor: 41.582

4. Latent TGFbeta1 overexpression in keratinocytes results in a severe psoriasis-like skin disorder.

Authors: Allen G Li; Donna Wang; Xin-Hua Feng; Xiao-Jing Wang
Journal: EMBO J Date: 2004-04-01 Impact factor: 11.598

5. Expression of transforming growth factor type beta on human epidermal dendritic cells.

Authors: M S Gruschwitz; O P Hornstein
Journal: J Invest Dermatol Date: 1992-07 Impact factor: 8.551

6. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease.

Authors: M M Shull; I Ormsby; A B Kier; S Pawlowski; R J Diebold; M Yin; R Allen; C Sidman; G Proetzel; D Calvin
Journal: Nature Date: 1992-10-22 Impact factor: 49.962

Review 7. Transforming growth factor-beta regulation of immune responses.

Authors: Ming O Li; Yisong Y Wan; Shomyseh Sanjabi; Anna-Karin L Robertson; Richard A Flavell
Journal: Annu Rev Immunol Date: 2006 Impact factor: 28.527

8. TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells.

Authors: Julien C Marie; John J Letterio; Marc Gavin; Alexander Y Rudensky
Journal: J Exp Med Date: 2005-04-04 Impact factor: 14.307

9. The integrin alpha(v)beta8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-beta1.

Authors: Dezhi Mu; Stephanie Cambier; Lars Fjellbirkeland; Jody L Baron; John S Munger; Hisaaki Kawakatsu; Dean Sheppard; V Courtney Broaddus; Stephen L Nishimura
Journal: J Cell Biol Date: 2002-04-22 Impact factor: 10.539

10. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis.

Authors: Vissia Viglietta; Clare Baecher-Allan; Howard L Weiner; David A Hafler
Journal: J Exp Med Date: 2004-04-05 Impact factor: 14.307

5 in total

1. Targeted deletion of TGFβ1 in basal keratinocytes causes profound defects in stratified squamous epithelia and aberrant melanocyte migration.

Authors: Fiona E Chalmers; Justyn E Dusold; Javed A Shaik; Hailey A Walsh; Adam B Glick
Journal: Dev Biol Date: 2022-02-25 Impact factor: 3.582

2. Competition for Active TGFβ Cytokine Allows for Selective Retention of Antigen-Specific Tissue- Resident Memory T Cells in the Epidermal Niche.

Authors: Toshiro Hirai; Yi Yang; Yukari Zenke; Haiyue Li; Virendra K Chaudhri; Jacinto S De La Cruz Diaz; Paul Yifan Zhou; Breanna Anh-Thu Nguyen; Laurent Bartholin; Creg J Workman; David W Griggs; Dario A A Vignali; Harinder Singh; David Masopust; Daniel H Kaplan
Journal: Immunity Date: 2020-11-18 Impact factor: 31.745

Keratinocyte-derived TGFβ is not required to maintain skin immune homeostasis.

1. Control of murine hair follicle regression (catagen) by TGF-beta1 in vivo.

2. Epidermal langerhans cell-deficient mice develop enhanced contact hypersensitivity.

3. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis.

4. Latent TGFbeta1 overexpression in keratinocytes results in a severe psoriasis-like skin disorder.

5. Expression of transforming growth factor type beta on human epidermal dendritic cells.

6. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease.

Review 7. Transforming growth factor-beta regulation of immune responses.

8. TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells.

9. The integrin alpha(v)beta8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-beta1.

10. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis.

1. Targeted deletion of TGFβ1 in basal keratinocytes causes profound defects in stratified squamous epithelia and aberrant melanocyte migration.

2. Competition for Active TGFβ Cytokine Allows for Selective Retention of Antigen-Specific Tissue- Resident Memory T Cells in the Epidermal Niche.

Review 3. TGF-β: Many Paths to CD103⁺ CD8 T Cell Residency.

4. Keratinocytes Regulate the Threshold of Inflammation by Inhibiting T Cell Effector Functions.

Review 5. Regulation of barrier immunity and homeostasis by integrin-mediated transforming growth factor β activation.

Review 7. Transforming growth factor-beta regulation of immune responses.

Review 3. TGF-β: Many Paths to CD103+ CD8 T Cell Residency.

Review 5. Regulation of barrier immunity and homeostasis by integrin-mediated transforming growth factor β activation.

Review 3. TGF-β: Many Paths to CD103⁺ CD8 T Cell Residency.