Human CD4+ FOXP3+ regulatory T cells produce CXCL8 and recruit neutrophils.
One of the defining features of the majority of FOXP3(+) Tregs is their inability to produce typical T-cell-derived cytokines. Little is known, however, about their capacity to produce chemokines. As Tregs are constitutively present in, and rapidly traffic to, non-lymphoid tissues, we hypothesized that they may produce chemokines to direct the composition of cells that infiltrate inflamed tissues. Surprisingly, we found that Tregs produce high amounts of CXCL8 (IL-8), a potent neutrophil chemoattractant. Tregs also produced other CC and CXC family chemokines, including CCL2-5, CCL7, and CXCL10. Whereas ectopic expression of FOXP3 suppressed cytokine production, it significantly induced CXCL8. Moreover, supernatants from Tregs attracted neutrophils via a CXCL8-dependent mechanism. These data provide the first evidence that although classical Tregs are defined by their lack of proinflammatory cytokine production, they secrete significant quantities of chemokines and thus may have an unappreciated role in directing the recruitment of immune cells.
Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
Megan E
ME
Himmel
Sarah Q
SQ
Crome
Sabine
S
Ivison
Ciriaco
C
Piccirillo
Theodore S
TS
Steiner
Megan K
MK
Levings
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D019742:Chemokines, CC / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D014161:Transduction, Genetic
D000911:Antibodies, Monoclonal; C508606:CXCL8 protein, human; D019742:Chemokines, CC; D019743:Chemokines, CXC; D017077:Culture Media, Conditioned; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D016209:Interleukin-8