Dysfunctional γδ T cells contribute to impaired keratinocyte homeostasis in mouse models of obesity.
Dysfunctional γδ T cells contribute to impaired keratinocyte homeostasis in mouse models of obesity.
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DOI：
10.1038/jid.2011.241
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发表时间：
2011-12
影响因子：
6.5
通讯作者：
Jameson, Julie M.
中科院分区：
文献类型：
--
作者：
Taylor, Kristen R.;Costanzo, Anne E.;Jameson, Julie M.
皮肤并发症和慢性不愈合伤口在肥胖症、代谢性疾病和2型糖尿病中很常见。表皮γδ T细胞通常产生角质形成细胞生长因子，参与伤口修复，并且是角质形成细胞稳态所必需的。我们已经确定，在γδ T细胞缺陷型小鼠中，角质形成细胞的数量减少，表皮表现出扁平、较薄的结构，基底角质形成细胞较少。这在肥胖症中很重要，其中皮肤驻留的γδ T细胞减少并导致功能障碍。与γδ T细胞缺陷小鼠相似，在两种肥胖小鼠模型中，角质形成细胞减少，表皮结构改变。即使在存在γδ T细胞的区域中，肥胖小鼠中的角质形成细胞也较少，表明功能失调的γδ T细胞不能调节角质形成细胞稳态。在肥胖症中，由于E-钙粘蛋白定位和表达另外改变，γδ T细胞缺失或受损对表皮结构的影响加剧。这些研究表明，γδ T细胞不能调节肥胖症中的角质形成细胞稳态，并且肥胖环境通过改变细胞-细胞粘附进一步损害皮肤结构。总之，通过直接和间接机制受损的角质形成细胞稳态和表皮屏障功能导致对皮肤并发症、慢性伤口和感染的易感性。
Skin complications and chronic non-healing wounds are common in obesity, metabolic disease and type 2 diabetes. Epidermal γδ T cells normally produce keratinocyte growth factors, participate in wound repair and are necessary for keratinocyte homeostasis. We have determined that in γδ T cell-deficient mice, there are reduced numbers of keratinocytes and the epidermis exhibits a flattened, thinner structure with fewer basal keratinocytes. This is important in obesity, where skin-resident γδ T cells are reduced and rendered dysfunctional. Similar to γδ T cell-deficient mice, keratinocytes are reduced and the epidermal structure is altered in two obese mouse models. Even in regions where γδ T cells are present, there are fewer keratinocytes in obese mice indicating that dysfunctional γδ T cells are unable to regulate keratinocyte homeostasis. The impact of absent or impaired γδ T cells on epidermal structure is exacerbated in obesity as E-cadherin localization and expression is additionally altered. These studies reveal that γδ T cells are unable to regulate keratinocyte homeostasis in obesity and that the obese environment further impairs skin structure by altering cell-cell adhesion. Together, impaired keratinocyte homeostasis and epidermal barrier function through direct and indirect mechanisms results in susceptibility to skin complications, chronic wounds and infection.
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影响因子：
4
作者：
Dejana, Elisabetta;Orsenigo, Fabrizio;Lampugnani, Maria Grazia
通讯作者：
Lampugnani, Maria Grazia
影响因子：
15.3
作者：
Toulon, Antoine;Breton, Lionel;Havran, Wendy L.
通讯作者：
Havran, Wendy L.
影响因子：
4.4
作者：
Jameson, JM;Cauvi, G;Havran, WL
通讯作者：
Havran, WL
影响因子：
6.5
作者：
Girardi, Michael;Lewis, Julia M.;Tigelaar, Robert E.
通讯作者：
Tigelaar, Robert E.
DOI：
10.4049/jimmunol.0902733
发表时间：
2010-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Havran WL;Jameson JM
通讯作者：
Jameson JM