Kinetics of Regulatory T Cells in the Ovalbumin Asthma Model in the Rat

Jurawitz, Marie-Charlot; Lührmann, Anke; Tschernig, Thomas; Pabst, Reinhard

doi:10.1159/000176302

Cited by 6 publications

(9 citation statements)

References 72 publications

(51 reference statements)

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“…[18][19][20] SAA is elevated within the same time-frame of accumulation of T reg during tissue injury. 21,22 Together with our in vivo data, these observations are consistent with the possibility that early induction of SAA at inflammatory sites, coupled with its effects on innate immune cells, generates a milieu that drives T reg proliferation. Our study also suggests that modulating the level of expression of SOCS3 in T reg and, consequentially, the relative expression of SOCS3 in T reg versus T eff by pharmacologic means abrogates the selective activation of mitogenic signaling pathways in T reg on exposure to the micro-environment generated by interaction between SAA and monocytes.…”

Section: Discussionsupporting

confidence: 86%

Serum amyloid A overrides Treg anergy via monocyte-dependent and Treg-intrinsic, SOCS3-associated pathways

Nguyen

Macaubas

Nadeau

et al. 2011

Blood

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IntroductionInflammation is a highly regulated physiologic response that has evolved as a mechanism to respond to infection as well as to promote healing in settings such as tissue injury. CD4 ϩ regulatory T cells (T reg ) are observed at sites of acute and chronic inflammation, 1,2 raising questions as to the molecular basis of their accumulation at these sites. Initial evidence suggested that immunosuppressive activities of T reg are diminished in the presence of inflammatory signals. 3,4 However, in several studies, the apparently opposite picture emerged, wherein T reg exposed to inflammatory signals retain potent suppressive activity. For instance, murine T reg at sites of viral infection or isolated from inflamed tissues still mediate regulatory function, 5-7 as do human T reg isolated from rheumatoid joints or inflamed colonic mucosa. 8,9 Collectively, these results point to the possibility that certain signals associated with inflammation might promote T reg activity. Here we unexpectedly identified serum amyloid A (SAA), an acute indicator of inflammation, as a novel factor that induces cellular and cytokine conditions to support the expansion of T reg while maintaining their suppressive capacity. MethodsIn vivo effects of SAA on T reg proliferation C57BL6/J mice (male, 8-10 weeks old) were purchased from Jackson Laboratory. Mice were injected intraperitoneally with recombinant human SAA (Peprotech, 30 g in 100 l PBS), purified human serum albumin (Sigma-Aldrich, 30 g in 100 l PBS), or endotoxin (Sigma-Aldrich, 0.25 ng in 100 l PBS). Animals were killed 16 hours later; peritoneal cells were harvested and stained for surface and intracellular markers to detect T reg frequency and proliferation. In vivo depletion of monocytes was performed with clodronate liposomes (Encapsula). In these experiments, 400 L of clodronate or empty liposomes were injected intraperitoneally 24 hours before SAA injection. Flow cytometry and ELISADetection of surface markers and intracellular molecules was performed. Antibodies to mouse and human proteins used in these experiments are purchased from Biolegend except for anti-human formyl peptide receptor like-1 (FPRL-1; R&D Systems), anti-human RAGE (receptor of advanced glycation end products), supressor of cytokine signaling 3 (SOCS3; Abcam), and anti-Ki-67, anti-human-pAKT (phosphonylated protein kinase B), pERK1/2 (phosphorylated extracellular signal regulated kinases 1 and 2; BD Biosciences). For in vitro experiments, the relevant subset was labeled with CFSE before suppression assays. Cells were pelleted at various time points and underwent standard staining protocols of the manufacturers. For in vivo experiments, cells were harvested from peritoneal cavity and underwent flow cytometric analysis.To detect cytokines in the plasma, cytometric bead arrays (BD Biosciences) and ELISA (R&D Systems) were used according to manufacturers' protocols. Human plasma preparationThe study was approved by the Institutional Review Board at Stanford University. All subjects provided inform...

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Section: Discussionsupporting

confidence: 86%

Serum amyloid A overrides Treg anergy via monocyte-dependent and Treg-intrinsic, SOCS3-associated pathways

Nguyen

Macaubas

Nadeau

et al. 2011

Blood

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“…By 24 h, the number of tracheal CD4 + CD25 + cells, but not CD4 + CD25 + Foxp3 + cells, had significantly increased in all mice (Figs 1g and h), and supports the conclusion that UV‐induced T regulatory cells were not responsible for reduced AHR. A further aerosol challenge may be required for the appearance of sufficient regulatory cells; in a study of the OVA asthma model in the rat, a second OVA challenge was required to detect a significant increase in T regulatory cells in lung tissue [12].…”

Section: Discussionmentioning

confidence: 99%

UV inhibits allergic airways disease in mice by reducing effector CD4⁺ T cells

McGlade

Strickland

Lambert

et al. 2010

Clin Experimental Allergy

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“…Treg cells are generated in mucosal DLNs in response to repeated antigen challenge and accumulate progressively thereafter in the airway mucosa [20,50]. The maintenance of airway mucosal Treg cell activity in this context is linked to continuing antigen exposure, because antigen withdrawal results in rapid return to baseline Treg numbers in the mucosa [20].…”

Section: Reviewmentioning

confidence: 99%