CCR10 and its ligands in regulation of epithelial immunity and diseases

Abstract

Epithelial tissues covering the external and internal surface of a body are constantly under physical, chemical or biological assaults. To protect the epithelial tissues and maintain their homeostasis, multiple layers of immune defense mechanisms are required. Besides the epithelial tissue-resident immune cells that provide the first line of defense, circulating immune cells are also recruited into the local tissues in response to challenges. Chemokines and chemokine receptors regulate tissue-specific migration, maintenance and functions of immune cells. Among them, chemokine receptor CCR10 and its ligands chemokines CCL27 and CCL28 are uniquely involved in the epithelial immunity. CCL27 is expressed predominantly in the skin by keratinocytes while CCL28 is expressed by epithelial cells of various mucosal tissues. CCR10 is expressed by various subsets of innate-like T cells that are programmed to localize to the skin during their developmental processes in the thymus. Circulating T cells might be imprinted by skin-associated antigen-presenting cells to express CCR10 for their recruitment to the skin during the local immune response. On the other hand, IgA antibody-producing B cells generated in mucosa-associated lymphoid tissues express CCR10 for their migration and maintenance at mucosal sites. Increasing evidence also found that CCR10/ligands are involved in regulation of other immune cells in epithelial immunity and are frequently exploited by epithelium-localizing or -originated cancer cells for their survival, proliferation and evasion from immune surveillance. Herein, we will review current knowledge on roles of CCR10/ligands in regulation of epithelial immunity and diseases and speculate on related important questions worth further investigation.

Adaptive immunity to murine skin commensals

“…Because CCR10 directs skin migration of T cells via its ligand CCL27 (reviewed in ref. 34) perhaps these T cells first migrate to skin, then to lymph nodes via draining lymphatics, along with DCs. How CCR10 is induced on peripheral T cells has not been examined.…”

Lymphocyte subsets contribute to the degree of lobulitis and ductitis in sclerosing lymphocytic lobulitis of the breast

“…Epithelial cells in the mammary gland can produce chemokine CCL28. Its receptor, CCR10, can be found in several T-cell subsets, but limited to the IgA antibody secreting subset in B cells 26. Moreover, intraepithelial T lymphocytes could play a primary role leading to the subsequent B-cell reaction and cytokine production, as in Hashimoto’s thyroiditis or Sjögren’s syndrome 19 22.…”

Chemokine receptors in allergic diseases

“…Its neutralization induces a decrease in the skin inflammation in a mouse model of atopic dermatitis (56). Moreover, its expression was controlled by the secretion of inflammatory cytokines, such as IL-1b and TNF-a, within inflamed tissues (57). Finally, the inhibition of CCL27 decreased inflammation and T-cell recruitment toward the skin (58).…”