Circulating regulatory T cells (Treg), leptin and induction of proinflammatory activity in obese Labrador Retriever dogs

Palatucci, Anna Teresa; Piantedosi, Diego; Rubino, Valentina; Giovazzino, Angela; Guccione, Jacopo; Pernice, Vlenia; Ruggiero, Giuseppina; Cortese, Laura; Terrazzano, Giuseppe

doi:10.1016/j.vetimm.2018.07.004

Cited by 10 publications

(14 citation statements)

References 57 publications

(67 reference statements)

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“…CD4 + CD25 +/high T cells are enriched for suppressive FoxP3 + T cells in humans and mice 33–35 . Our previous work has shown that canine CD4 + CD25 high T cells induced in vitro are regulatory 31 , but studies examining these cells ex vivo are limited in number and scope 36–38 . We therefore set out to characterise canine CD4 + CD25 high T cells isolated ex vivo , hypothesising that they possess regulatory phenotype and function.…”

Section: Introductionmentioning

confidence: 99%

Phenotypic characterisation of regulatory T cells in dogs reveals signature transcripts conserved in humans and mice

Chang

Stell

et al. 2019

Sci Rep

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Regulatory T cells (Tregs) are a double-edged regulator of the immune system. Aberrations of Tregs correlate with pathogenesis of inflammatory, autoimmune and neoplastic disorders. Phenotypically and functionally distinct subsets of Tregs have been identified in humans and mice on the basis of their extensive portfolios of monoclonal antibodies (mAb) against Treg surface antigens. As an important veterinary species, dogs are increasingly recognised as an excellent model for many human diseases. However, insightful study of canine Tregs has been restrained by the limited availability of mAb. We therefore set out to characterise CD4+CD25high T cells isolated ex vivo from healthy dogs and showed that they possess a regulatory phenotype, function, and transcriptomic signature that resembles those of human and murine Tregs. By launching a cross-species comparison, we unveiled a conserved transcriptomic signature of Tregs and identified that transcript hip1 may have implications in Treg function.

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Section: Introductionmentioning

confidence: 99%

Phenotypic characterisation of regulatory T cells in dogs reveals signature transcripts conserved in humans and mice

Chang

Stell

et al. 2019

Sci Rep

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“…It is of note that serum leptin level in obese subjects at T0 was higher than that in the CTR dogs, while it was reduced at T1 assuming values comparable to those of the CTR subjects (Table 4 and Figure 8G). In this context, an inverse leptin and Treg cell correlation (90,91) is usually recorded in humans, although there is no definitive evidence on this phenomenon in dogs (37). It is conceivable that a longer period of WLP, with the persisting normal level of leptin, could also generate the Treg recover.…”

Section: The Immune Profile Of Enrolled Dogs Upon Wlpmentioning

confidence: 96%

“…Treg cells inversely correlate with serum leptin (35) and are significantly reduced in serum samples of obese humans (36). Palatucci et al (37) described the inverse relationship between the concentration of leptin in serum and circulating Treg levels in obese Labrador Retrievers, suggesting a high similarity with human obesity (35).…”

Section: Introductionmentioning

confidence: 99%

Effect of a Weight Loss Program on Biochemical and Immunological Profile, Serum Leptin Levels, and Cardiovascular Parameters in Obese Dogs

et al. 2020

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This study aimed to investigate the effects of a weight loss program (WLP) on biochemical and immunological profile, and cardiovascular parameters in a cohort of dogs with naturally occurring obesity. Eleven obese dogs [body condition scoring (BCS), ≥7/9] were enrolled into the study and underwent clinical and cardiovascular examination, and blood testing before (T0) and after 6 months (T1) of WLP. Eleven normal weight (BCS, 4/5) healthy dogs were used as a control (CTR) group. Compared to the CTR group, at T0 obese dogs expressed higher serum leptin concentrations (p < 0.0005) that significantly decreased after weight loss (p < 0.005) but remained higher than the CTR group. Furthermore, obese dogs showed considerably lower levels (p < 0.0005) of regulatory T cell (Treg) compared to the CTR group, but they did not change after weight loss at T1. In obese dogs, tumor necrosis factor (TNF)-α and interleukin (IL)-6 concentrations were substantially reduced at T1 (p < 0.0001 and p < 0.005). Regarding the cardiovascular parameters, only one obese dog was hypertensive at T0, and systolic blood pressure values showed no significant differences at the end of the WLP. The ratio of interventricular septal thickness in diastole to left ventricle internal diameter in diastole (IVSd/LVIDd) was significantly greater in obese dogs at T0 than in the CTR group (p < 0.005). It decreased after weight loss (p < 0.05). In obese dogs, troponin I level significantly reduced with weight loss (p < 0.05), while endothelin-1 level did not differ statistically. The results suggest that the immune dysregulation in the presence of high leptin levels and reduced number of Treg could affect obese dogs as well as humans. Based on our findings, we may speculate that a more complete immune-regulation restore could be obtained by a greater reduction in fat mass and a longer-term WLP. Finally, left ventricular remodeling may occur in some obese dogs. Piantedosi et al. Effects of Weight Loss in Dogs However, in canine species, further studies are needed to investigate the impact of obesity and related WLP on cardiovascular system.

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“…Therefore, an excess of nutrients could drive the immune system towards self-reactivity, while a defect can determine insufficient anti-infectious immune responses. In this regard, the relationship between obesity and immune modulation appears of great relevance in both human and veterinary medicine [7,56,57,62,63,64,65,66,67].…”

Section: Role Of Leptin In the Relationship Between Obesity And Immentioning

confidence: 99%

“…Palatucci et al [65] reported that obese Labrador Retrievers are characterized by the inverse correlation between leptin serum concentration and circulating Treg levels. Moreover, an increased number of cytotoxic T cell effectors and a higher IFN-γ production by cytotoxic T lymphocytes have been observed in obese dogs [65]. However, the relationship between obesity, leptin, and circulating Treg level, as well as the occurrence of systemic inflammation in dogs and in other domestic mammalians are still poorly understood.…”

Section: Role Of Leptin In the Relationship Between Obesity And Immentioning

confidence: 99%

Leptin and Immunological Profile in Obesity and Its Associated Diseases in Dogs

Cortese

Terrazzano

Pelagalli

2019

IJMS

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Growing scientific evidence has unveiled increased incidences of obesity in domestic animals and its influence on a plethora of associated disorders. Leptin, an adipokine regulating body fat mass, represents a key molecule in obesity, able to modulate immune responses and foster chronic inflammatory response in peripheral tissues. High levels of cytokines and inflammatory markers suggest an association between inflammatory state and obesity in dogs, highlighting the parallelism with humans. Canine obesity is a relevant disease always accompanied with several health conditions such as inflammation, immune-dysregulation, insulin resistance, pancreatitis, orthopaedic disorders, cardiovascular disease, and neoplasia. However, leptin involvement in many disease processes in veterinary medicine is poorly understood. Moreover, hyperleptinemia as well as leptin resistance occur with cardiac dysfunction as a consequence of altered cardiac mitochondrial metabolism in obese dogs. Similarly, leptin dysregulation seems to be involved in the pancreatitis pathophysiology. This review aims to examine literature concerning leptin and immunological status in obese dogs, in particular for the aspects related to obesity-associated diseases.

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Circulating regulatory T cells (Treg), leptin and induction of proinflammatory activity in obese Labrador Retriever dogs

Cited by 10 publications

References 57 publications

Phenotypic characterisation of regulatory T cells in dogs reveals signature transcripts conserved in humans and mice

Phenotypic characterisation of regulatory T cells in dogs reveals signature transcripts conserved in humans and mice

Effect of a Weight Loss Program on Biochemical and Immunological Profile, Serum Leptin Levels, and Cardiovascular Parameters in Obese Dogs

Leptin and Immunological Profile in Obesity and Its Associated Diseases in Dogs

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