In:
The Journal of Immunology, The American Association of Immunologists, Vol. 196, No. 1_Supplement ( 2016-05-01), p. 117.3-117.3
Abstract:
The central feature of systemic lupus erythematosus (SLE) pathogenesis is loss of immunologic self-tolerance. Here, we address a current controversy regarding whether neutrophils influence the development of B cell auto-reactivity SLE. While both human and murine lupus neutrophils produce factors known to fuel adaptive immune dysregulation, including type I interferon, B cell survival factors, and extracellular traps (a putative source of self-antigen), some studies have contended that neutrophils in peripheral lymphoid organs (PLO) suppress B cell activation and differentiation. In order to ask whether neutrophils exert regulatory or deleterious effects on loss of B cell self-tolerance and immune activation, we compare changes in SLE progression following neutrophil depletion in the NZB/W lupus model, either during or after establishment of disease. Following depletion early in disease, we observe pronounced acceleration of proteinuria, anti-dsDNA titers, and germinal center formation. However, neutrophil depletion after onset of overt disease pathology (including proteinuria) does not strongly alter SLE progression, implicating neutrophils as playing a protective role only apparent during disease onset. To elucidate the specific mechanisms underlying neutrophil effects on B cell auto-reactivity, we examine the cytokine profile of neutrophils in direct proximity to B cells in PLO during several stages of disease. With progression of disease, we observe an influx of interferon-alpha-producing neutrophils in direct proximity to B cells in PLO. These data delineate a shifting balance of both regulatory and activating roles for neutrophils in auto-reactive B cell activation/proliferation during SLE progression.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.196.Supp.117.3
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2016
detail.hit.zdb_id:
1475085-5
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