| First Author | Kuo P | Year | 2018 |
| Journal | J Invest Dermatol | Volume | 138 |
| Issue | 6 | Pages | 1348-1359 |
| PubMed ID | 29277541 | Mgi Jnum | J:265688 |
| Mgi Id | MGI:6193261 | Doi | 10.1016/j.jid.2017.12.021 |
| Citation | Kuo P, et al. (2018) HPV16E7-Induced Hyperplasia Promotes CXCL9/10 Expression and Induces CXCR3(+) T-Cell Migration to Skin. J Invest Dermatol 138(6):1348-1359 |
| abstractText | Chemokines regulate tissue immunity by recruiting specific subsets of immune cells. Mice expressing the E7 protein of human papilloma virus 16 as a transgene from a keratin 14 promoter (K14.E7) show increased epidermal and dermal lymphocytic infiltrates, epidermal hyperplasia, and suppressed local immunity. Here, we show that CXCL9 and CXCL10 are overexpressed in non-hematopoietic cells in skin of K14.E7 mice when compared with non-transgenic animals, and recruit CXCR3(+) lymphocytes to the hyperplastic skin. Overexpression of CXCL9 and CXCL10 is not observed in E7 transgenic mice with mutated Rb gene whose protein product cannot interact with E7 (K14.E7xRb(DeltaL/DeltaL)) and in consequence lack hyperplastic epithelium. CXCR3(+) T cells are preferentially recruited by CXCL9 and CXCL10 in supernatants of K14.E7 but not K14.E7xRb(DeltaL/DeltaL) skin cultures in vitro. CXCR3 signalling promotes infiltration of a subset of effector T lymphocytes that enables donor lymphocyte deficient, E7-expressing skin graft rejection. Taken together, this suggests that recruitment of CXCR3(+) T cells can be an important factor in the rejection of precancerous skin epithelium providing they can overcome local immunosuppressive mechanisms driven by skin-resident lymphocytes. |
