NK depletion results in increased CCL22 secretion and Treg levels in Lewis lung carcinoma via the accumulation of CCL22-secreting CD11b+CD11c+ cells.
Tumor-induced immune suppression involves the accumulation of suppressive infiltrates in the tumor microenvironment such as regulatory T-cells (Tregs). Previous studies demonstrated that NK-dependant increases in CCL22 secretion selectively recruit Tregs toward murine lungs bearing Lewis Lung Carcinoma (LLC). To extend the in vitro studies, the present studies utilized in vivo depletion of NK cells to ascertain the contribution of NK-derived CCL22 toward total CCL22 and subsequent Treg levels in both normal and LLC-bearing lungs. However, NK depletion had the unexpected effect of increasing both CCL22 secretion and Treg levels in the lungs of NK-depleted LLC-bearing mice. This was concurrent with an increase in tumor burden. Flow cytometry and a series of both immunomagnetic and FACS isolations were used to identify the CCL22-producing cellular fractions in LLC-bearing lungs. A novel CD11b(+)CD11c(+) cell population was identified that accumulates in large numbers in NK-depleted LLC-bearing lung tissue. These CD11b(+)CD11c(+) cells secreted large amounts of CCL22 that may overcompensate for the loss of NK-derived CCL22 in the lungs of NK-depleted LLC-bearing mice. Taken together, these data suggest that NK cells play both a positive and negative role in the regulation of CCL22 secretion and, in turn, the recruitment of Tregs toward LLC-bearing lungs.
Mailloux
Adam W
AW
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
Clark
Anna-Maria A
AM
Young
M Rita I
MR
D000818:Animals; D039481:CD11b Antigen / Q000096:biosynthesis / Q000276:immunology*; D039521:CD11c Antigen / Q000096:biosynthesis / Q000276:immunology*; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D054422:Chemokine CCL22 / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005677:G(M1) Ganglioside / Q000037:antagonists & inhibitors / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
C515482:CCL22 protein, human; D039481:CD11b Antigen; D039521:CD11c Antigen; D054422:Chemokine CCL22; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside