CCR10 is a chemokine receptor. One of its ligand, CCL27, is predominantly expressed in the skin. The CCR10/ligand axis was suggested to play a role in directing migration and maintenance of CCR10-expressing T cells into the skin and has been implicated in many skin inflammatory diseases such as psoriasis and atopic dermatitis. However, the in vivo functional importance and mechanisms of CCR10 in regulating the cutaneous immune responses are still not clear. We have generated CCR10-knockout/EGFP-knockin mice and found that the CCR10-knockout mice have altered maintenance of skin-resident T cells and response to various skin antigen challenges. We propose to use these mouse models to study the functional mechanisms of CCR10 in regulating the skin T response and immune homeostasis.
Public Health Narrative Many skin diseases such as inflammatory diseases and cancers are due to or involve the dysregulated immune response in the skin. Understanding how the immune system in the skin is regulated is critical to developing efficient treatment against the skin inflammation diseases and other dysfunctions. Findings from our proposed study on roles of an important skin-homing molecule CCR10 in regulating the skin T cell response will aid our understanding of molecular mechanisms regulating the skin immune response and development of therapeutic targets in treatment of the skin inflammation diseases.
|Fu, Yaoyao; Yang, Jie; Xiong, Na (2016) Cutting Edge: Skin CCR10+ CD8+ T Cells Support Resident Regulatory T Cells through the B7.2/Receptor Axis To Regulate Local Immune Homeostasis and Response. J Immunol 196:4859-64|
|Yang, Jie; Hu, Shaomin; Zhao, Luming et al. (2016) Selective programming of CCR10(+) innate lymphoid cells in skin-draining lymph nodes for cutaneous homeostatic regulation. Nat Immunol 17:48-56|
|Xiong, Na; Hu, Shaomin (2015) Regulation of intestinal IgA responses. Cell Mol Life Sci 72:2645-55|