Novel role of regulatory T cells in limiting early neutrophil responses in skin.
It is clear that CD4(+)  CD25(+)  Foxp3(+) regulatory T (Treg) cells inhibit chronic inflammatory responses as well as adaptive immune responses. Among the CD4(+) T-cell population in the skin, at least one-fifth express Foxp3. As the skin is constantly exposed to antigenic challenge and is a common site of vaccination, understanding the role of these skin-resident Treg cells is important. Although the suppressive effect of Treg cells on T cells is well documented, less is known about the types of innate immune cells influenced by Treg cells and whether the Treg cells suppress acute innate immune responses in vivo. To address this we used a mouse melanoma cell line expressing Fas ligand (B16FasL), which induces an inflammatory response following subcutaneous injection of mice. We demonstrate that Treg cells limit this response by inhibiting neutrophil accumulation and survival within hours of tumour cell inoculation. This effect, which was associated with decreased expression of the neutrophil chemoattractants CXCL1 and CXCL2, promoted survival of the inoculated tumour cells. Overall, these data imply that Treg cells in the skin are rapidly mobilized and that this activity serves to limit the amplification of inflammatory responses at this site.
Richards
Hannah
H
Infection, Immunity and Biochemistry, School of Medicine, Heath Park, Cardiff , UK.
Williams
Anwen
A
Jones
Emma
E
Hindley
James
J
Godkin
Andrew
A
Simon
Anna Katharina
AK
Gallimore
Awen
A
D000818:Animals; D045744:Cell Line, Tumor; D054360:Chemokine CXCL1 / Q000276:immunology; D054426:Chemokine CXCL2 / Q000276:immunology; D053222:Fas Ligand Protein / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology; D007113:Immunity, Innate; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D051379:Mice; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D012867:Skin / Q000276:immunology* / Q000473:pathology; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D013997:Time Factors
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse