SCID mouse model of psoriasis

A unique tool for drug development of autoreactive T-cell and TH-17 cell-mediated autoimmune diseases

Smriti K. Raychaudhuri, Siba P Raychaudhuri

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

In both skin and synovial tissues of psoriatic arthritis (PsA) patients, there are prominent lymphocytic infiltrates localized to the dermal papillae in the skin and the sublining layer stroma in the joint. T-cells, with a predominance of CD4+ lymphocytes, are the most significant lymphocytes in the tissues; in contrast, this ratio is reversed in the epidermis, synovial fluid compartment, and at the enthesis, where CD8+ T-cells are more common. This differential tropism of CD8+ T-cell suggests that the CD8+ T-cells may be driving the immune response in the joint and skin. This is supported by an association with MHC class I. The cytokine network in the psoriatic skin and synovium is dominated by monocyte and T-cell-derived cytokines: IL-1, IL-2, IL-10, IFN-, and TNF-. In PsA synovium, higher levels of IFN-, IL-2, and IL-10 have been detected than in psoriatic skin. An analysis of T-cell receptor beta-chain variable (TCRV) gene repertoires revealed common expansions in both skin and synovial inflammatory sites, suggesting an important role for cognate T-cell responses in the pathogenesis of PsA and that the inciting antigen may be identical or homologous between the afflicted skin and synovium. Traditionally, T-cells have been classified as T helper 1 (Th1) or Th2 cells by production of defining cytokines, IFN- and IL-4, respectively. Recently, a new type of T-cell, Th17, has been linked to autoimmune inflammation. T-helper 17 (Th17) cells are a unique effector CD4+ T-cell subset characterized by the production of interleukin (IL)-17. Murine diseases that were previously considered to be pure Th1-mediated responses have been shown to contain mixed populations of Th1 and Th17 cells. Also, in humans, a critical immunoregulatory role of Th-17 cells in infectious and autoimmune diseases has been identified. It has been postulated that IL-17 may be important in psoriasis. Our initial observations demonstrate that IL-17 and its receptor system are important for PsA also. In in vivo and in vitro studies we have demonstrated that IL-17/IL-17R are enriched in skin, synovial tissue, and synovial fluid of psoriatic arthritis patients and Th17 cells are functionally significant in the pathogenesis of psoriasis and psoriatic arthritis. Here we will share our experience of the SCID mouse model of psoriasis in respect to its use in investigating psoriatic diseases and development of immune-based drugs for psoriasis, psoriatic arthritis, and other autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)157-160
Number of pages4
JournalIndian Journal of Dermatology
Volume55
Issue number2
DOIs
StatePublished - Apr 1 2010

Fingerprint

Th17 Cells
SCID Mice
Psoriasis
Psoriatic Arthritis
Autoimmune Diseases
T-Lymphocytes
Skin
Pharmaceutical Preparations
Interleukin-17
Synovial Membrane
Synovial Fluid
Cytokines
Interleukin-10
Interleukin-2
Interleukin-17 Receptors
Joints
T-Cell Receptor beta Genes
Lymphocytes
Th2 Cells
Th1 Cells

Keywords

  • Novel therapy
  • Psoriasis
  • Psoriatic arthritis
  • SCID mouse
  • Th17 cell

ASJC Scopus subject areas

  • Dermatology

Cite this

SCID mouse model of psoriasis : A unique tool for drug development of autoreactive T-cell and TH-17 cell-mediated autoimmune diseases. / Raychaudhuri, Smriti K.; Raychaudhuri, Siba P.

In: Indian Journal of Dermatology, Vol. 55, No. 2, 01.04.2010, p. 157-160.

Research output: Contribution to journalArticle

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