Acquisition of antigen-presenting functions by neutrophils isolated from mice with chronic colitis.
Active episodes of the inflammatory bowel diseases are associated with the infiltration of large numbers of myeloid cells including neutrophils, monocytes, and macrophages. The objective of this study was to systematically characterize and define the different populations of myeloid cells generated in a mouse model of chronic gut inflammation. Using the T cell transfer model of chronic colitis, we found that induction of disease was associated with enhanced production of myelopoietic cytokines (IL-17 and G-CSF), increased production of neutrophils and monocytes, and infiltration of large numbers of myeloid cells into the mesenteric lymph nodes (MLNs) and colon. Detailed characterization of these myeloid cells revealed three major populations including Mac-1(+)Ly6C(high)Gr-1(low/neg) cells (monocytes), Mac-1(+)Ly6C(int)Gr-1(+) cells (neutrophils), and Mac-1(+)Ly6C(low/neg)Gr-1(low/neg) leukocytes (macrophages, dendritic cells, and eosinophils). In addition, we observed enhanced surface expression of MHC class II and CD86 on neutrophils isolated from the inflamed colon when compared with neutrophils obtained from the blood, the MLNs, and the spleen of colitic mice. Furthermore, we found that colonic neutrophils had acquired APC function that enabled these granulocytes to induce proliferation of OVA-specific CD4(+) T cells in an Ag- and MHC class II-dependent manner. Finally, we observed a synergistic increase in proinflammatory cytokine and chemokine production following coculture of T cells with neutrophils in vitro. Taken together, our data suggest that extravasated neutrophils acquire APC function within the inflamed bowel where they may perpetuate chronic gut inflammation by inducing T cell activation and proliferation as well as by enhancing production of proinflammatory mediators.
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
Dmitry V
DV
Ostanin
Elvira
E
Kurmaeva
Katie
K
Furr
Richard
R
Bao
Jason
J
Hoffman
Seth
S
Berney
Matthew B
MB
Grisham
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D049109:Cell Proliferation; D002908:Chronic Disease; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D018836:Inflammation Mediators; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D018836:Inflammation Mediators