On the model-based design of front-to-total anti-roll moment distribution controllers for yaw rate tracking

In passenger cars active suspensions have been traditionally used to enhance comfort through body control, and handling through the reduction of the tyre load variations induced by road irregularities. However, active suspensions can also be designed to track a desired yaw rate profile through the control of the anti-roll moment distribution between the front and rear axles. The effect of the anti-roll moment distribution relates to the nonlinearity of tyre behaviour, which is difficult to capture in the linearised vehicle models normally used for control design. Hence, the tuning of anti-roll moment distribution controllers is usually based on heuristics. This paper includes an analysis of the effect of the lateral load transfer on the lateral axle force and cornering stiffness. A linearised axle force formulation is presented, and compared with a formulation from the literature, based on a quadratic relationship between cornering stiffness and load transfer. Multiple linearised vehicle models for control design are assessed in the frequency domain, and the respective controllers are tuned through optimisation routines. Simulation results from a nonlinear vehicle model are discussed to analyse the performance of the controllers, and show the importance of employing accurate models of the lateral load transfer effect during control design

On the model-based design of front-to-total anti-roll moment distribution controllers for yaw rate tracking

In passenger cars active suspensions have been traditionally used to enhance comfort through body control, and handling through the reduction of the tyre load variations induced by road irregularities. However, active suspensions can also be designed to track a desired yaw rate profile through the control of the anti-roll moment distribution between the front and rear axles. The effect of the anti-roll moment distribution relates to the nonlinearity of tyre behaviour, which is difficult to capture in the linearised vehicle models normally used for control design. Hence, the tuning of anti-roll moment distribution controllers is usually based on heuristics. This paper includes an analysis of the effect of the lateral load transfer on the lateral axle force and cornering stiffness. A linearised axle force formulation is presented, and compared with a formulation from the literature, based on a quadratic relationship between cornering stiffness and load transfer. Multiple linearised vehicle models for control design are assessed in the frequency domain, and the respective controllers are tuned through optimisation routines. Simulation results from a nonlinear vehicle model are discussed to analyse the performance of the controllers, and show the importance of employing accurate models of the lateral load transfer effect during control design

Regulation of gut inflammation and TH17 cell response by interleukin-21

Background & Aims: Interleukin (IL)-21, a T-cell-derived cytokine, is overproduced in inflammatory bowel diseases (IBD), but its role in the pathogenesis of gut inflammation remains unknown. We here examined whether IL-21 is necessary for the initiation and progress of experimental colitis and whether it regulates specific pathways of inflammation. Methods: Both dextran sulfate sodium colitis and trinitrobenzene sulfonic acid-relapsing colitis were induced in wild-type and IL-21-deficient mice. CD4+CD25- T cells from wild-type and IL-21-deficient mice were differentiated in T helper cell (Th)17-polarizing conditions, with or without IL-21 or an antagonistic IL-21R/Fc. We also examined whether blockade of IL-21 by anti-IL-21 antibody reduced IL-17 in cultures of IBD lamina propria CD3+ T lymphocytes. Cytokines were evaluated by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay. Results: High IL-21 was seen in wild-type mice with dextran sulfate sodium- and trinitrobenzene sulfonic acid-relapsing colitis. IL-21-deficient mice were largely protected against both colitides and were unable to up-regulate Th17-associated molecules during gut inflammation, thus suggesting a role for IL-21 in controlling Th17 cell responses. Indeed, na\uefve T cells from IL-21-deficient mice failed to differentiate into Th17 cells. Treatment of developing Th17 cells from wild-type mice with IL-21R/Fc reduced IL-17 production. Moreover, in the presence of transforming growth factor-\u3b21, exogenous IL-21 substituted for IL-6 in driving IL-17 induction. Neutralization of IL-21 reduced IL-17 secretion by IBD lamina propria lymphocytes. Conclusions: These results indicate that IL-21 is a critical regulator of inflammation and Th17 cell responses in the gut

Regulation of gut inflammation and th17 cell response by interleukin-21

Background & Aims: Interleukin (IL)-21, a T-cell-derived cytokine, is overproduced in inflammatory bowel diseases (IBD), but its role in the pathogenesis of gut inflammation remains unknown. We here examined whether IL-21 is necessary for the initiation and progress of experimental colitis and whether it regulates specific pathways of inflammation. Methods: Both dextran sulfate sodium colitis and trinitrobenzene sulfonic acid-relapsing colitis were induced in wild-type and IL-21-deficient mice. CD4+CD25 12 T cells from wild-type and IL-21-deficient mice were differentiated in T helper cell (Th)17-polarizing conditions, with or without IL-21 or an antagonistic IL-21R/Fc. We also examined whether blockade of IL-21 by anti-IL-21 antibody reduced IL-17 in cultures of IBD lamina propria CD3+ T lymphocytes. Cytokines were evaluated by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay. Results: High IL-21 was seen in wild-type mice with dextran sulfate sodium- and trinitrobenzene sulfonic acid-relapsing colitis. IL-21-deficient mice were largely protected against both colitides and were unable to up-regulate Th17-associated molecules during gut inflammation, thus suggesting a role for IL-21 in controlling Th17 cell responses. Indeed, na\uefve T cells from IL-21-deficient mice failed to differentiate into Th17 cells. Treatment of developing Th17 cells from wild-type mice with IL-21R/Fc reduced IL-17 production. Moreover, in the presence of transforming growth factor-\u3b21, exogenous IL-21 substituted for IL-6 in driving IL-17 induction. Neutralization of IL-21 reduced IL-17 secretion by IBD lamina propria lymphocytes. Conclusions: These results indicate that IL-21 is a critical regulator of inflammation and Th17 cell responses in the gut

Regulation of gut inflammation and Th17 cell response by interleukin-21

Background & Aims: Interleukin (IL)-21, a T-cell-derived cytokine, is overproduced in inflammatory bowel diseases (1111)), but its role in the pathogenesis of gut inflammation remains unknown. We here examined whether IL-21 is necessary for the initiation and progress of experimental colitis and whether it regulates specific pathways of inflammation. Methods: Both dextran sulfate sodium colitis and trinitrobenzene sulfonic acid-relapsing colitis were induced in wild-type and IL-21-deficient mice. CD4(+)CD25(-) T cells from wild-type and IL-21-deficient mice were differentiated in T helper cell (Th) 17-polarizing conditions, with or without IL-21 or an antagonistic IL-21R/Fc. We also examined whether blockade of IL-21 by anti-IL-21 antibody reduced IL-17 in cultures of IBD lamina propria CD3(+) T lymphocytes. Cytokines were evaluated by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay. Result : High IL-21 was seen in wild-type mice with dextran sulfate sodium- and trinitrobenzene sulfonic acid-relapsing colitis. IL-21-deficient mice were largely protected against both colitides and were unable to up-regulate Th17-associated molecules during gut inflammation, thus suggesting a role for IL-21 in controlling Th17 cell responses. Indeed, naive T cells from IL-21-deficient mice failed to differentiate into Th17 cells. Treatment of developing Th17 cells from wild-type mice with IL-21R/Fc reduced IL-17 production. Moreover, in the presence of transforming growth factor-beta 1, exogenous IL-21 substituted for IL-6 in driving IL-17 induction. Neutralization of IL-21 reduced IL-17 secretion by IBD lamina propria lymphocytes. Conclusions: These results indicate that IL-21 is a critical regulator of inflammation and Th17 cell responses in the gut

Regulation of gut inflammation and th17 cell response by interleukin-21

Background & Aims: Interleukin (IL)-21, a T-cell-derived cytokine, is overproduced in inflammatory bowel diseases (IBD), but its role in the pathogenesis of gut inflammation remains unknown. We here examined whether IL-21 is necessary for the initiation and progress of experimental colitis and whether it regulates specific pathways of inflammation. Methods: Both dextran sulfate sodium colitis and trinitrobenzene sulfonic acid-relapsing colitis were induced in wild-type and IL-21-deficient mice. CD4+CD25− T cells from wild-type and IL-21-deficient mice were differentiated in T helper cell (Th)17-polarizing conditions, with or without IL-21 or an antagonistic IL-21R/Fc. We also examined whether blockade of IL-21 by anti-IL-21 antibody reduced IL-17 in cultures of IBD lamina propria CD3+ T lymphocytes. Cytokines were evaluated by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay. Results: High IL-21 was seen in wild-type mice with dextran sulfate sodium- and trinitrobenzene sulfonic acid-relapsing colitis. IL-21-deficient mice were largely protected against both colitides and were unable to up-regulate Th17-associated molecules during gut inflammation, thus suggesting a role for IL-21 in controlling Th17 cell responses. Indeed, naïve T cells from IL-21-deficient mice failed to differentiate into Th17 cells. Treatment of developing Th17 cells from wild-type mice with IL-21R/Fc reduced IL-17 production. Moreover, in the presence of transforming growth factor-β1, exogenous IL-21 substituted for IL-6 in driving IL-17 induction. Neutralization of IL-21 reduced IL-17 secretion by IBD lamina propria lymphocytes. Conclusions: These results indicate that IL-21 is a critical regulator of inflammation and Th17 cell responses in the gut

Regulation of gut inflammation and TH17 cell response by interleukin-21

Background & Aims: Interleukin (IL)-21, a T-cell-derived cytokine, is overproduced in inflammatory bowel diseases (IBD), but its role in the pathogenesis of gut inflammation remains unknown. We here examined whether IL-21 is necessary for the initiation and progress of experimental colitis and whether it regulates specific pathways of inflammation. Methods: Both dextran sulfate sodium colitis and trinitrobenzene sulfonic acid-relapsing colitis were induced in wild-type and IL-21-deficient mice. CD4+CD25- T cells from wild-type and IL-21-deficient mice were differentiated in T helper cell (Th)17-polarizing conditions, with or without IL-21 or an antagonistic IL-21R/Fc. We also examined whether blockade of IL-21 by anti-IL-21 antibody reduced IL-17 in cultures of IBD lamina propria CD3+ T lymphocytes. Cytokines were evaluated by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay. Results: High IL-21 was seen in wild-type mice with dextran sulfate sodium- and trinitrobenzene sulfonic acid-relapsing colitis. IL-21-deficient mice were largely protected against both colitides and were unable to up-regulate Th17-associated molecules during gut inflammation, thus suggesting a role for IL-21 in controlling Th17 cell responses. Indeed, na\uefve T cells from IL-21-deficient mice failed to differentiate into Th17 cells. Treatment of developing Th17 cells from wild-type mice with IL-21R/Fc reduced IL-17 production. Moreover, in the presence of transforming growth factor-\u3b21, exogenous IL-21 substituted for IL-6 in driving IL-17 induction. Neutralization of IL-21 reduced IL-17 secretion by IBD lamina propria lymphocytes. Conclusions: These results indicate that IL-21 is a critical regulator of inflammation and Th17 cell responses in the gut