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- Title
CCL17-producing cDC2s are essential in end-stage lupus nephritis and averted by a parasitic infection.
- Authors
Amo, Laura; Kole, Hemanta K.; Scott, Bethany; Chen-Feng Qi; Juan Wu; Bolland, Silvia; Qi, Chen-Feng; Wu, Juan
- Abstract
Lupus nephritis is a severe organ manifestation in systemic lupus erythematosus leading to kidney failure in a subset of patients. In lupus-prone mice, controlled infection with Plasmodium parasites protects against the progression of autoimmune pathology including lethal glomerulonephritis. Here, we demonstrate that parasite-induced protection was not due to a systemic effect of infection on autoimmunity as previously assumed, but rather to specific alterations in immune cell infiltrates into kidneys and renal draining lymph nodes. Infection of lupus-prone mice with a Plasmodium parasite did not reduce the levels or specificities of autoreactive antibodies, vasculitis, immune complex-induced innate activation, or hypoxia. Instead, infection uniquely reduced kidney-infiltrating CCL17-producing bone marrow-derived type 2 inflammatory dendritic cells (iDC2s). Bone marrow reconstitution experiments revealed that infection with Plasmodium caused alterations in bone marrow cells that hindered the ability of DC2s to infiltrate the kidneys. The essential role for CCL17 in lupus nephritis was confirmed by in vivo depletion with a blocking antibody, which reduced kidney pathology and immune infiltrates, while bypassing the need for parasitic infection. Therefore, infiltration into the kidneys of iDC2s, with the potential to prime local adaptive responses, is an essential regulated event in the transition from manageable glomerulonephritis to lethal tubular injury.
- Subjects
PARASITIC diseases; LUPUS nephritis; BONE marrow cells; NEPHRITIS; SYSTEMIC lupus erythematosus; KIDNEY failure; BONE marrow; CYTOKINES; PROTOZOA; DENDRITIC cells; BIOLOGICAL models; MALARIA; ANIMALS; MICE
- Publication
Journal of Clinical Investigation, 2021, Vol 131, Issue 11, p1
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI148000