Interleukin-17A Promotes Early but Attenuates Established Disease in Crescentic Glomerulonephritis in Mice

Odobasic, Dragana; Gan, Poh-Yi; Summers, Shaun A.; Semple, T.J.; Muljadi, Ruth; Iwakura, Yoichiro; Kitching, A. Richard; Holdsworth, Stephen R.

doi:10.1016/j.ajpath.2011.05.039

Cited by 49 publications

(53 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[18][19][20] In glomerulonephritis, a biphasic response with protection against renal injury in the early phase and aggravation in the later phase was found in IL-17-deficient mice. 21 A protective effect of IL-17 has also been suggested in aortic aneurysm formation, and low circulating IL-17 levels were associated with a higher cardiovascular risk after myocardial infarction. 22,23 IL-17 deficiency is not equivalent to inhibiting Th17 cell generation.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of the Interleukin 17/23 Axis Accelerates Renal Injury in Mice With Deoxycorticosterone Acetate+Angiotensin II–Induced Hypertension

et al. 2014

View full text Add to dashboard Cite

R ecent data suggest that hypertension and hypertensive end-organ damage are not only mediated by hemodynamic injury but also by innate and adaptive immune responses. 1 In their seminal article, Guzik et al 2 were able to show that RAG-1 -/-mice that lack T and B cells have attenuated hypertension in response to angiotensin II (Ang II) infusion. This finding was confirmed in SCID mice. 3 In 2005, a novel T-helper cell subset (Th17) producing interleukin 17 (IL-17) was discovered.4 IL-17 is a proinflammatory cytokine secreted by innate and adaptive immune cells. Although the source of IL-17 is restricted to hematopoietic cells, the IL-17 receptor is widely expressed. Th17 cells need interleukin 23 (IL-23) for expansion and survival. IL-23 is secreted by activated dendritic cells and macrophages. The potential function of Th17 cells in autoimmune disease was first shown in IL-23p19-deficient mice. IL-23p19 knockout animals demonstrated a substantial decrease in Th17-polarized cells and were resistant to the development of experimental autoimmune encephalomyelitis, 5 experimental induction of multiple sclerosis, and rheumatoid arthritis. A new link between cardiovascular disease and IL-17 has been proposed by recent data showing that increased dietary salt intake drives autoimmune diseases through the induction of Th17 cells. C57black mice are resistant to hypertensive end-organ damage. 7 We recently showed that combining deoxycorticosterone acetate (DOCA) salt and Ang II infusion induces substantial hypertensive renal and cardiac injury. 8 This model has been successfully used to evaluate the role of chemokine receptors and ADMA (asymmetric dimethylarginine) in hypertensive end-organ damage.

show abstract

Section: Discussionmentioning

confidence: 99%

Deficiency of the Interleukin 17/23 Axis Accelerates Renal Injury in Mice With Deoxycorticosterone Acetate+Angiotensin II–Induced Hypertension

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Paust et al demonstrated that Th17 cells contributes to anti-GBM GN with the use of IL-23p192/2 and IL-17A2/2 mice (87), whereas Odobasic et al examined the reciprocal relationship between Th1 and Th17 and demonstrated that early nephritogenic responses were mediated by Th17 cells, but late disease is Th1 dependent. They also demonstrated that each Th subset counterregulated the other (88). Furthermore, Steinmetz et al used mice with gene deletion of RORg-t, the key Th17 transcription factor, to confirm the participation of the CD41 Th17 subset (89).…”

Section: Autoimmune Crescentic Glomerulonephritis Lupus Nephritismentioning

confidence: 99%

Cytokines

Holdsworth

Gan

2015

Clinical Journal of the American Society of Nephrology

Self Cite

117

View full text Add to dashboard Cite

Cytokines play an important role in host defense against microorganisms. They orchestrate innate immunity by inducing protective local inflammation and systemic acute phase responses. Cytokines are important in initiating, amplifying, directing, mediating, and regulating adaptive immunity. Unfortunately, they may also direct tissue damage if excessive responses occur or if they are involved in directing and mediating autoimmunity. Under these circumstances, cytokines are potential therapeutic targets. Over the last 20 years, we have seen the successful development and clinical implementation of biologic strategies that target key cytokines in specific inflammatory diseases with efficacy, specificity, and toxicity profiles challenging conventional drug therapies. These therapies are finding new applications and many new agents show promise. Unfortunately, these new cytokine-based therapies have had little effect on renal disease. This review provides evidence that common renal diseases, including those causing AKI and the autoimmune proliferative and crescentic forms of GN, have cytokine mediation profiles that suggest they would be susceptible to cytokine-targeting therapeutic strategies.

show abstract

“…First, T H 17 cells and, subsequently, T H 1 cells migrate into the kidney and promote renal tissue injury. [11][12][13] The role of neutrophils in the T cellmediated phase (starting from day 5) is largely unknown. We therefore assessed the time course of renal neutrophil infiltration using immunohistochemical staining for the neutrophil marker Gr1 (Ly6C/Ly6G) ( Figure 1A).…”

Section: Time-and Compartment-specific Infiltration Of Neutrophils Inmentioning

confidence: 99%

CXCL5 Drives Neutrophil Recruitment in TH17-Mediated GN

Disteldorf¹,

Krebs²,

Paust³

et al. 2015

Journal of the American Society of Nephrology

112

View full text Add to dashboard Cite

Neutrophil trafficking to sites of inflammation is essential for the defense against bacterial and fungal infections, but also contributes to tissue damage in T H 17-mediated autoimmunity. This process is regulated by chemokines, which often show an overlapping expression pattern and function in pathogen-and autoimmune-induced inflammatory reactions. Using a murine model of crescentic GN, we show that the pathogenic T H 17/IL-17 immune response induces chemokine (C-X-C motif) ligand 5 (CXCL5) expression in kidney tubular cells, which recruits destructive neutrophils that contribute to renal tissue injury. By contrast, CXCL5 was dispensable for neutrophil recruitment and effective bacterial clearance in a murine model of acute bacterial pyelonephritis. In line with these findings, CXCL5 expression was highly upregulated in the kidneys of patients with ANCA-associated crescentic GN as opposed to patients with acute bacterial pyelonephritis. Our data therefore identify CXCL5 as a potential therapeutic target for the restriction of pathogenic neutrophil infiltration in T H 17-mediated autoimmune diseases while leaving intact the neutrophil function in protective immunity against invading pathogens.

show abstract

Interleukin-17A Promotes Early but Attenuates Established Disease in Crescentic Glomerulonephritis in Mice

Cited by 49 publications

References 54 publications

Deficiency of the Interleukin 17/23 Axis Accelerates Renal Injury in Mice With Deoxycorticosterone Acetate+Angiotensin II–Induced Hypertension

Deficiency of the Interleukin 17/23 Axis Accelerates Renal Injury in Mice With Deoxycorticosterone Acetate+Angiotensin II–Induced Hypertension

Cytokines

CXCL5 Drives Neutrophil Recruitment in TH17-Mediated GN

Contact Info

Product

Resources

About