title: Regulatory T cells prevent inducible BALT formation by dampening neutrophilic inflammation.
abstract: Inducible BALT (iBALT) can amplify pulmonary or systemic inflammatory responses to the benefit or detriment of the host. We took advantage of the age-dependent formation of iBALT to interrogate the underlying mechanisms that give rise to this ectopic, tertiary lymphoid organ. In this study, we show that the reduced propensity for weanling as compared with neonatal mice to form iBALT in response to acute LPS exposure is associated with greater regulatory T cell expansion in the mediastinal lymph nodes. Ab- or transgene-mediated depletion of regulatory T cells in weanling mice upregulated the expression of IL-17A and CXCL9 in the lungs, induced a tissue neutrophilia, and increased the frequency of iBALT to that observed in neonatal mice. Remarkably, neutrophil depletion in neonatal mice decreased the expression of the B cell active cytokines, a proliferation-inducing ligand and IL-21, and attenuated LPS-induced iBALT formation. Taken together, our data implicate a role for neutrophils in lymphoid neogenesis. Neutrophilic inflammation is a common feature of many autoimmune diseases in which iBALT are present and pathogenic, and hence the targeting of neutrophils or their byproducts may serve to ameliorate detrimental lymphoid neogenesis in a variety of disease contexts.
authors: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales 2308, Australia;
authors: Shen Yun
authors: SY
authors: Foo
authors: School of Biomedical Sciences, University of Queensland, St. Lucia, Queensland 4072, Australia;
authors: Vivian
authors: V
authors: Zhang
authors: School of Biomedical Sciences, University of Queensland, St. Lucia, Queensland 4072, Australia;
authors: Amit
authors: A
authors: Lalwani
authors: School of Biomedical Sciences, University of Queensland, St. Lucia, Queensland 4072, Australia;
authors: Jason P
authors: JP
authors: Lynch
authors: School of Biomedical Sciences, University of Queensland, St. Lucia, Queensland 4072, Australia;
authors: Aowen
authors: A
authors: Zhuang
authors: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales 2308, Australia;
authors: Chuan En
authors: CE
authors: Lam
authors: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales 2308, Australia;
authors: Paul S
authors: PS
authors: Foster
authors: Department of Immunology, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia;
authors: Cecile
authors: C
authors: King
authors: Diamantina Institute, University of Queensland, Woolloongabba, Queensland 4102, Australia;
authors: Raymond J
authors: RJ
authors: Steptoe
authors: School of Biomedical Sciences, University of Queensland, St. Lucia, Queensland 4072, Australia;
authors: Stuart B
authors: SB
authors: Mazzone
authors: Queensland Children's Medical Research Institute, University of Queensland, Herston, Queensland 4006, Australia; and Australian Infectious Diseases Research Centre, University of Queensland, St. Lucia, Queensland 4006, Australia.
authors: Peter D
authors: PD
authors: Sly
authors: School of Biomedical Sciences, University of Queensland, St. Lucia, Queensland 4072, Australia; Australian Infectious Diseases Research Centre, University of Queensland, St. Lucia, Queensland 4006, Australia s.phipps@uq.edu.au.
authors: Simon
authors: S
authors: Phipps
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D060833:Cellular Microenvironment / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D008212:Lymphocyte Depletion; D008221:Lymphoid Tissue / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13