T cell plasticity in renal autoimmune disease

TY - JOUR

T1 - T cell plasticity in renal autoimmune disease

AU - Soukou, Shiwa

AU - Huber, Samuel

AU - Krebs, Christian F

PY - 2021/8

Y1 - 2021/8

N2 - The presence of immune cells is a morphological hallmark of rapidly progressive glomerulonephritis, a disease group that includes anti-glomerular basement membrane glomerulonephritis, lupus nephritis, and anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. The cellular infiltrates include cells from both the innate and the adaptive immune responses. The latter includes CD4+ and CD8+ T cells. In the past, CD4+ T cell subsets were viewed as terminally differentiated lineages with limited flexibility. However, it is now clear that Th17 cells can in fact have a high degree of plasticity and convert, for example, into pro-inflammatory Th1 cells or anti-inflammatory Tr1 cells. Interestingly, Th17 cells in experimental GN display limited spontaneous plasticity. Here we review the literature of CD4+ T cell plasticity focusing on immune-mediated kidney disease. We point out the key findings of the past decade, in particular that targeting pathogenic Th17 cells by anti-CD3 injection can be a tool to modulate the CD4+ T cell response. This anti-CD3 treatment can trigger a regulatory phenotype in Th17 cells and transdifferentiation of Th17 cells into immunosuppressive IL-10-expressing Tr1 cells (Tr1exTh17 cells). Thus, targeting Th17 cell plasticity could be envisaged as a new therapeutic approach in patients with glomerulonephritis.

AB - The presence of immune cells is a morphological hallmark of rapidly progressive glomerulonephritis, a disease group that includes anti-glomerular basement membrane glomerulonephritis, lupus nephritis, and anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. The cellular infiltrates include cells from both the innate and the adaptive immune responses. The latter includes CD4+ and CD8+ T cells. In the past, CD4+ T cell subsets were viewed as terminally differentiated lineages with limited flexibility. However, it is now clear that Th17 cells can in fact have a high degree of plasticity and convert, for example, into pro-inflammatory Th1 cells or anti-inflammatory Tr1 cells. Interestingly, Th17 cells in experimental GN display limited spontaneous plasticity. Here we review the literature of CD4+ T cell plasticity focusing on immune-mediated kidney disease. We point out the key findings of the past decade, in particular that targeting pathogenic Th17 cells by anti-CD3 injection can be a tool to modulate the CD4+ T cell response. This anti-CD3 treatment can trigger a regulatory phenotype in Th17 cells and transdifferentiation of Th17 cells into immunosuppressive IL-10-expressing Tr1 cells (Tr1exTh17 cells). Thus, targeting Th17 cell plasticity could be envisaged as a new therapeutic approach in patients with glomerulonephritis.

U2 - 10.1007/s00441-021-03466-z

DO - 10.1007/s00441-021-03466-z

M3 - SCORING: Review article

C2 - 33937944

VL - 385

SP - 323

EP - 333

JO - CELL TISSUE RES

JF - CELL TISSUE RES

SN - 0302-766X

IS - 2

ER -