Title: |
Psoriasis-like Inflammation Induced in an Air-pouch Mouse Model. |
Authors: |
CHARITIDIS, FILIPPOS T., DAMLUND, DINA S. M., KOCH, JANNE |
Source: |
In Vivo; Jul/Aug2021, Vol. 35 Issue 4, p1985-1997, 13p |
Subject Terms: |
PSORIASIS, INFLAMMATION, T helper cells, CYTOKINES, LABORATORY mice |
Abstract: |
Background/Aim: The pathway of initiation of psoriasis comprises the differentiation and infiltration of Thelper 17 (Th17) cells into the skin, characterized by the production of interleukin 17A and 17F (IL-17A/IL-17F) among other cytokines, resulting in a downstream cascade of events. Due to the lack of simplicity in psoriasis models, we aimed to develop an easily and rapidly inducible mouse model for the IL-23/IL-17 pathway with quick readouts from a straightforward lavaging process and with detectable cytokine levels. Materials and Methods: We utilized the 6-day airpouch mouse model, injected with a combination of anti-CD3, IL-23 and IL-1β. At 24, 48 and 72 h, intra-pouch secretion of IL-17A, IL-17F and C-X-C motif chemokine ligand 1 were measured. Skin biopsies were collected and immune cell infiltration evaluated, and intra-pouch immune cells were isolated and analyzed. Results: The combination of anti-CD3, IL-23 with and without IL-1β significantly increased intrapouch levels of IL-17A/IL-17F at 24 and 72 h, triggering a downstream production of C-X-C motif chemokine ligand 1. The cytokines were detectable even 72 h post-induction. T-cell receptor beta was down-regulated on CD4+ and CD8+ T-cells, indicating intra-pouch T-cell activation. anti-CD3 induced CD3+ cell migration into the subcutis and the lining tissue surrounding the cavity of the air pouch, where in the latter, a similar distribution pattern of Il17a mRNA-expressing cells was also observed. However, no Th17 cell differentiation nor changes in IL-17A+ granulocytes were observed. Conclusion: The induced air-pouch mouse model induced with a cocktail of anti-CD3, IL-23 with or without IL-1β is able to mirror the IL-23/IL-17 axis of psoriasis-like inflammation characterized by immune cell infiltration and cytokine secretion. [ABSTRACT FROM AUTHOR] |
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Database: |
Complementary Index |