IL-12, independently of IFN-gamma, plays a crucial role in the pathogenesis of a murine psoriasis-like skin disorder - PubMed (original) (raw)
Comparative Study
. 1999 Jun 15;162(12):7480-91.
Affiliations
- PMID: 10358203
Comparative Study
IL-12, independently of IFN-gamma, plays a crucial role in the pathogenesis of a murine psoriasis-like skin disorder
K Hong et al. J Immunol. 1999.
Abstract
The onset of acute psoriasis and the exacerbation of chronic psoriasis are often associated with a history of bacterial infection. We demonstrate that while only few scid/scid mice develop disease when CD4+CD45Rbhigh T cells are transferred alone, coadministration of LPS plus IL-12 or staphylococcal enterotoxin B into scid/scid mice 1 day after CD4+CD45Rbhigh T cell transfer greatly enhances disease penetrance and severity. Most importantly, the skin lesions induced by this method exhibit many of the histologic hallmarks observed in human psoriasis. Skin infiltrating CD4+ T cells were predominantly memory/effector cells (CD45Rblow) and exhibited a highly polarized Th1 phenotype. To test whether the development of pathogenic T cells was dependent on their production of IFN-gamma, we transferred IFN-gamma-/- CD4+CD45Rbhigh T cells into scid/scid or into T, B and NK cell-deficient scid/beige mice. Surprisingly, the incidence of psoriasis was similar to scid/scid animals that received IFN-gamma+/+ T cells, although acanthosis of the skin was attenuated. In contrast, the development of psoriasis was abolished if anti-IL-12 mAb was administered on day 7 and 35 after T cell transfer. Skin-derived IFN-gamma-/- inflammatory cells, but not cells from anti-IL-12-treated animals, secreted substantial amounts of TNF-alpha, suggesting that the inflammatory effect of IFN-gamma-/- T cells may be partly exerted by TNF-alpha and that the therapeutic effect of anti-IL-12 may depend on its ability to down-regulate both TNF-alpha and IFN-gamma. Overall, these results suggest that IL-12, independently of IFN-gamma, is able to induce pathogenic, inflammatory T cells that are able to induce psoriasiform lesions in mice.
Similar articles
- Colitis-inducing potency of CD4+ T cells in immunodeficient, adoptive hosts depends on their state of activation, IL-12 responsiveness, and CD45RB surface phenotype.
Claesson MH, Bregenholt S, Bonhagen K, Thoma S, Möller P, Grusby MJ, Leithäuser F, Nissen MH, Reimann J. Claesson MH, et al. J Immunol. 1999 Mar 15;162(6):3702-10. J Immunol. 1999. PMID: 10092833 - Tissue specificity of E- and P-selectin ligands in Th1-mediated chronic inflammation.
Chu A, Hong K, Berg EL, Ehrhardt RO. Chu A, et al. J Immunol. 1999 Nov 1;163(9):5086-93. J Immunol. 1999. PMID: 10528215 - IL-12, but not IFN-gamma, plays a major role in sustaining the chronic phase of colitis in IL-10-deficient mice.
Davidson NJ, Hudak SA, Lesley RE, Menon S, Leach MW, Rennick DM. Davidson NJ, et al. J Immunol. 1998 Sep 15;161(6):3143-9. J Immunol. 1998. PMID: 9743382 - Is psoriasis induced by streptococcal superantigens and maintained by M-protein-specific T cells that cross-react with keratin?
Valdimarsson H, Sigmundsdóttir H, Jónsdóttir I. Valdimarsson H, et al. Clin Exp Immunol. 1997 Jan;107 Suppl 1:21-4. Clin Exp Immunol. 1997. PMID: 9020931 Review. - Regulation of the inflammatory response in animal models of multiple sclerosis by interleukin-12.
Leonard JP, Waldburger KE, Schaub RG, Smith T, Hewson AK, Cuzner ML, Goldman SJ. Leonard JP, et al. Crit Rev Immunol. 1997;17(5-6):545-53. Crit Rev Immunol. 1997. PMID: 9419442 Review.
Cited by
- Proteomic and Metabolomic Changes in Psoriasis Preclinical and Clinical Aspects.
Radulska A, Pelikant-Małecka I, Jendernalik K, Dobrucki IT, Kalinowski L. Radulska A, et al. Int J Mol Sci. 2023 May 30;24(11):9507. doi: 10.3390/ijms24119507. Int J Mol Sci. 2023. PMID: 37298466 Free PMC article. Review. - IFN-κ Is a Rheostat for Development of Psoriasiform Inflammation.
Gharaee-Kermani M, Estadt SN, Tsoi LC, Wolf-Fortune SJ, Liu J, Xing X, Theros J, Reed TJ, Lowe L, Gruszka D, Ward NL, Gudjonsson JE, Kahlenberg JM. Gharaee-Kermani M, et al. J Invest Dermatol. 2022 Jan;142(1):155-165.e3. doi: 10.1016/j.jid.2021.05.029. Epub 2021 Aug 5. J Invest Dermatol. 2022. PMID: 34364883 Free PMC article. - Immune responses and therapeutic options in psoriasis.
Afonina IS, Van Nuffel E, Beyaert R. Afonina IS, et al. Cell Mol Life Sci. 2021 Mar;78(6):2709-2727. doi: 10.1007/s00018-020-03726-1. Epub 2021 Jan 2. Cell Mol Life Sci. 2021. PMID: 33386888 Free PMC article. Review. - Adaptive and Innate Immunity in Psoriasis and Other Inflammatory Disorders.
Schön MP. Schön MP. Front Immunol. 2019 Jul 26;10:1764. doi: 10.3389/fimmu.2019.01764. eCollection 2019. Front Immunol. 2019. PMID: 31402919 Free PMC article. Review. - Three Constituents of Moringa oleifera Seeds Regulate Expression of Th17-Relevant Cytokines and Ameliorate TPA-Induced Psoriasis-Like Skin Lesions in Mice.
Ma N, Tang Q, Wu WT, Huang XA, Xu Q, Rong GL, Chen S, Song JP. Ma N, et al. Molecules. 2018 Dec 10;23(12):3256. doi: 10.3390/molecules23123256. Molecules. 2018. PMID: 30544700 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources
Medical
Molecular Biology Databases
Research Materials