By Eleanor McDermid, Senior medwireNews Reporter
The absence of a protein called Ctip2 in the skin allows increased levels of T-helper 2 (Th-2) cytokines and may have a role in conditions such as atopic dermatitis (AD), research in mice suggests.
This strengthens the evidence for a crucial epidermal role for Ctip2, which is already known to play a critical part in epidermal proliferation and terminal differentiation, and barrier formation.
"The skin's ability to resist inflammation is going down just as the amount of inflammation is going up, and the underlying reason is that Ctip2 is not doing its job," explained lead study author Arup Indra (Oregon State University, Corvallis, USA) in a press statement.
Indra and team found that thymic stromal lymphopoietin (TSLP), which they describe as a "master initiator of Th2 inflammatory responses," was significantly upregulated in mice lacking Ctip2 in their epidermal cells. It was upregulated about 30-fold as early as postnatal day 1, relative to levels in wild-type mice, and was upregulated about 1000-fold from 1 month after birth.
Ctip2 directly interacted with the distal region of the TSLP promoter in chromatin immunoprecipitation assays, "suggesting Ctip2 may directly repress TSLP transcription in mouse keratinocytes," report the researchers in PLoS One.
As anticipated, a number of Th2 cytokines were significantly upregulated in the skin of the mice lacking Ctip2, including the chemokine CCL17 and the interleukins 13, 4, 6, and 10, whereas Th1 and Th17 cytokines were not upregulated.
The clinical effects of Ctip2 deletion included spontaneous dermatitis and progressive alopecia in almost all of the mice by the age of 4 months. On detailed analysis, they had increased transepidermal water loss, significant epidermal hyperplasia, and increased infiltration of inflammatory cells in the skin.
Deletion of Ctip2 also had systemic consequences. Mice lacking the protein had elevated plasma levels of TSLP and several Th2 cytokines, relative to wild-type mice, and at the age of 4 months they also had increased levels of immunoglobulin E and the Th1 cytokine tumor necrosis factor α. These mice also had inguinal lymphadenopathy, a small, convoluted thymus, and progressive splenomegaly.
This systemic response "could possibly lead to inflammation of airway and pulmonary epithelium and asthma," suggests the team.
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