CXCR3+ Regulatory T Cells Control TH1 Responses in Crescentic GN

Paust, Hans‐Joachim; Riedel, Jan-Hendrik; Krebs, Christian; Turner, Jan-Eric; Brix, Silke R.; Krohn, Sonja; Velden, Joachim; Wiech, Thorsten; Kaffke, Anna; Peters, Anett; Bennstein, Sabrina Bianca; Kapffer, Sonja; Meyer-Schwesinger, Catherine; Wegscheid, Claudia; Tiegs, Gisa; Thaiss, Friedrich; Mittrücker, Hans‐Willi; Steinmetz, Oliver M.; Stahl, Rolf A.K.; Panzer, Ulf

doi:10.1681/asn.2015020203

Cited by 74 publications

(84 citation statements)

References 41 publications

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“…T‐bet is a critical regulator of Th1 differentiation, and controls Th1 cell cytokine production or migration by regulating the expression of chemokines and their receptors . Tregs are generally viewed as a suppressor of Th1 immune responses in various inflammatory diseases . However, our finding contradicts the result acquired by Liu et al .…”

Section: Discussioncontrasting

confidence: 82%

Regulatory T‐cells promote pulmonary repair by modulating T helper cell immune responses in lipopolysaccharide‐induced acute respiratory distress syndrome

et al. 2019

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Summary Acute respiratory distress syndrome (ARDS) induces a strong local infiltration of regulatory T‐cells (Tregs) in the lungs. However, at present, there remains a lack of adequate evidence showing the direct effect of Tregs on pulmonary repair and the related mechanisms of ARDS. Therefore, in this project, we studied the impact of Tregs on lipopolysaccharide (LPS)‐induced ARDS and pulmonary inflammation. Surprisingly, we found that depletion of Tregs by injection of PC61 anti‐CD25 antibody not only interfered with the inflammation resolution, such as inhibited total cell infiltration into the alveolar space, downregulated neutrophils, upregulated macrophages, but also impaired pulmonary epithelium and endothelial cell proliferation. Consistent with the attenuation of pulmonary repair, we found that the Th1 and Th17 immune responses were also impaired in Treg‐depleted mice, suggesting that the presence of Tregs is vital for tissue repair, as Tregs modulate and promote the Th immune response in LPS‐induced pulmonary inflammation.

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Section: Discussioncontrasting

confidence: 82%

Regulatory T‐cells promote pulmonary repair by modulating T helper cell immune responses in lipopolysaccharide‐induced acute respiratory distress syndrome

et al. 2019

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“…There is also evidence that intrarenal CD103 + dendritic cells (<5% of renal DCs) support the development and retention of Tregs . Th1‐driven autoimmunity is a key feature of this disease model, and CXCR3 + and Tbet + Tregs have been shown to infiltrate the kidney and dampen specifically Th1‐driven glomerulonephritis . These data are consistent with more recent studies that demonstrate an essential role for Tbet + Tregs to suppress Th1‐driven autoimmunity .…”

Section: Regulatory T Cells In Autoimmune Glomerulonephritissupporting

confidence: 88%

“…This decrease in suppressive function of Tregs from AAV patients could be explained by the finding that Tregs from AAV patients preferentially express a splice variant of Foxp3 lacking exon 2 . Lastly, in kidney biopsies from AAV patients, CD4 + Foxp3 + Tregs expressing the chemokine receptor CXCR3 were recruited to the kidney and found in direct cell–cell contact with CXCR3 + Foxp3 − Th1 cells …”

Section: Regulatory T Cells In Autoimmune Glomerulonephritismentioning

confidence: 99%

Regulatory T cells in renal disease

et al. 2018

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The kidney is vulnerable to injury, both acute and chronic from a variety of immune and metabolic insults, all of which at least to some degree involve inflammation. Regulatory T cells modulate systemic autoimmune and allogenic responses in glomerulonephritis and transplantation. Intrarenal regulatory T cells (Tregs), including those recruited to the kidney, have suppressive effects on both adaptive and innate immune cells, and probably also intrinsic kidney cells. Evidence from autoimmune glomerulonephritis implicates antigen‐specific Tregs in HLA‐mediated dominant protection, while in several human renal diseases Tregs are abnormal in number or phenotype. Experimentally, Tregs can protect the kidney from injury in a variety of renal diseases. Mechanisms of Treg recruitment to the kidney include via the chemokine receptors CCR6 and CXCR3 and potentially, at least in innate injury TLR9. The effects of Tregs may be context dependent, with evidence for roles for immunoregulatory roles both for endogenous Tbet‐expressing Tregs and STAT‐3‐expressing Tregs in experimental glomerulonephritis. Most experimental work and some of the ongoing human trials in renal transplantation have focussed on unfractionated thymically derived Tregs (tTregs). However, induced Tregs (iTregs), type 1 regulatory T (Tr1) cells and in particular antigen‐specific Tregs also have therapeutic potential not only in renal transplantation, but also in other kidney diseases.

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“…Despite being a marker for pro-inflammatory T cells, CXCR3 may have unpredictable effects in renal disease as it also expressed on the immunosuppressive T regulatory cells that specifically temper the actions of Th1 cells (63). Three IFNG-inducible chemokine ligands bind CXCR3: CXCL9, CXCL10, and CXCL11.…”

Section: CXC Chemokinesmentioning

confidence: 99%

The role of chemokines in hypertension and consequent target organ damage

Rudemiller

Crowley

2017

Pharmacological Research

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Immune cells infiltrate the kidney, vasculature, and central nervous system during hypertension, consequently amplifying tissue damage and/or blood pressure elevation. Mononuclear cell motility depends partly on chemokines, which are small cytokines that guide cells through an increasing concentration gradient via ligation of their receptors. Tissue expression of several chemokines is elevated in clinical and experimental hypertension. Likewise, immune cells have enhanced chemokine receptor expression during hypertension, driving immune cell infiltration and inappropriate inflammation in cardiovascular control centers. T lymphocytes and monocytes/macrophages are pivotal mediators of hypertensive inflammation, and these cells migrate in response to several chemokines. As powerful drivers of diapedesis, the chemokines CCL2 and CCL5 have long been implicated in hypertension, but experimental data highlight divergent, context-specific effects of these chemokines on blood pressure and tissue injury. Several other chemokines, particularly those of the CXC family, contribute to blood pressure elevation and target organ damage. Given the significant interplay and chemotactic redundancy among chemokines during disease, future work must not only describe the actions of individual chemokines in hypertension, but also characterize how manipulating a single chemokine modulates the expression and/or function of other chemokines and their cognate receptors. This information will facilitate the design of precise chemotactic immunotherapies to limit cardiovascular and renal morbidity in hypertensive patients.

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CXCR3+ Regulatory T Cells Control TH1 Responses in Crescentic GN

Cited by 74 publications

References 41 publications

Regulatory T‐cells promote pulmonary repair by modulating T helper cell immune responses in lipopolysaccharide‐induced acute respiratory distress syndrome

Regulatory T‐cells promote pulmonary repair by modulating T helper cell immune responses in lipopolysaccharide‐induced acute respiratory distress syndrome

Regulatory T cells in renal disease

The role of chemokines in hypertension and consequent target organ damage

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