The BB/Wor Rat and the Balance Hypothesis of Autoimmunity

Mordes, John P.; Bortell, Rita; Doukas, John; Rigby, Mark R.; Whalen, Barbara J.; Zipris, Danny; Greiner, Dale L.; Rossini, Aldo A.

doi:10.1002/(sici)1099-0895(199607)12:2<103::aid-dmr157>3.0.co;2-2

Cited by 52 publications

(2 citation statements)

References 44 publications

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“…BB rats, which spontaneously develop T1D, thyroiditis, and other endocrinopathies, bear a profound lymphopenia, in contrast with KDP rats, which suffer from similar organ‐specific autoimmunity without lymphopenia (133, see above). The genetic defect responsible for lymphopenia in BB rats is a mutation of Ian5 , a member of the genes encoding the IAN (immune‐associated nucleotide‐binding protein) family of GTP‐binding proteins (134).…”

Section: Potential Imbalance Between Tregs and Self‐reactive T Cells mentioning

confidence: 99%

Foxp3⁺CD25⁺CD4⁺ natural regulatory T cells in dominant self‐tolerance and autoimmune disease

Sakaguchi

Ono

Setoguchi

et al. 2006

Immunological Reviews

1,416

1,063

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Naturally arising CD25+ CD4+ regulatory T (Treg) cells, most of which are produced by the normal thymus as a functionally mature T-cell subpopulation, play key roles in the maintenance of immunologic self-tolerance and negative control of a variety of physiological and pathological immune responses. Natural Tregs specifically express Foxp3, a transcription factor that plays a critical role in their development and function. Complete depletion of Foxp3-expressing natural Tregs, whether they are CD25+ or CD25-, activates even weak or rare self-reactive T-cell clones, inducing severe and widespread autoimmune/inflammatory diseases. Natural Tregs are highly dependent on exogenously provided interleukin (IL)-2 for their survival in the periphery. In addition to Foxp3 and IL-2/IL-2 receptor, deficiency or functional alteration of other molecules, expressed by T cells or non-T cells, may affect the development/function of Tregs or self-reactive T cells, or both, and consequently tip the peripheral balance between the two populations toward autoimmunity. Elucidation of the molecular and cellular basis of this Treg-mediated active maintenance of self-tolerance will facilitate both our understanding of the pathogenetic mechanism of autoimmune disease and the development of novel methods of autoimmune disease prevention and treatment via enhancing and re-establishing Treg-mediated dominant control over self-reactive T cells.

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Section: Potential Imbalance Between Tregs and Self‐reactive T Cells mentioning

confidence: 99%

Foxp3⁺CD25⁺CD4⁺ natural regulatory T cells in dominant self‐tolerance and autoimmune disease

Sakaguchi

Ono

Setoguchi

et al. 2006

Immunological Reviews

1,416

1,063

View full text Add to dashboard Cite

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“…DR lyp/lyp rats also develop spontaneous T1DM. Unless insulin is administered, death follows after T1DM onset as a result of hyperglycemia and ketoacidosis (Mordes et al, 1996). In BB rats, islet β cells express eotaxin (Geoffrey et al, 2006), which leads to infiltration of CCR3-expressing neutrophils and MCs to the pancreatic islets (Kukreja and Maclaren, 1999; Hessner et al, 2004).…”

Section: Role Of Mast Cells In Diabetes and Diabetic Complicationsmentioning

confidence: 99%

Different Roles of Mast Cells in Obesity and Diabetes: Lessons from Experimental Animals and Humans

Shi

2012

Front. Immun.

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Mast cells (MCs) play an important role in allergic hyperresponsiveness and in defending microorganism infections. Recent studies of experimental animals and humans have suggested that MCs participate in obesity and diabetes. MC distribution and activities in adipose tissues may vary, depending on the locations of different adipose tissues. In addition to releasing inflammatory mediators to affect adipose tissue extracellular matrix remodeling and to promote inflammatory cell recruitment and proliferation, MCs directly and indirectly interact and activate adipose tissue cells, including adipocytes and recruited inflammatory cells. Plasma MC protease levels are significantly higher in obese patients than in lean subjects. Experimental obese animals lose body weight after MC inactivation. MC functions in diabetes are even more complicated, and depend on the type of diabetes and on different diabetic complications. Both plasma MC proteases and MC activation essential immunoglobulin E levels are significant risk factors for human pre-diabetes and diabetes mellitus. MC stabilization prevents diet-induced diabetes and improves pre-established diabetes in experimental animals. MC depletion or inactivation can improve diet-induced type 2 diabetes and some forms of type 1 diabetes, but also can worsen other forms of type 1 diabetes, at least in experimental animals. Observations from animal and human studies have suggested beneficial effects of treating diabetic patients with MC stabilizers. Some diabetic patients may benefit from enhancing MC survival and proliferation – hypotheses that merit detailed basic researches and clinical studies.

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Thymic expression of insulin-related genes in an animal model of autoimmune type 1 diabetes

Kecha-Kamoun

Achour

Martens

et al. 2001

Diabetes Metab. Res. Rev.

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Background Insulin and multiple other autoantigens have been implicated in the pathogenesis of autoimmune type 1 diabetes, but the origin of immunological self-reactivity specifically oriented against insulin-secreting islet b-cells remains obscure. The primary objective of the present study was to investigate the hypothesis that a defect in thymic central T-cell selftolerance of the insulin hormone family could contribute to the pathophysiology of type 1 diabetes. This hypothesis was investigated in a classic animal model of type 1 diabetes, the Bio-Breeding (BB) rat.

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The BB/Wor Rat and the Balance Hypothesis of Autoimmunity

Cited by 52 publications

References 44 publications

Foxp3⁺CD25⁺CD4⁺ natural regulatory T cells in dominant self‐tolerance and autoimmune disease

Foxp3⁺CD25⁺CD4⁺ natural regulatory T cells in dominant self‐tolerance and autoimmune disease

Different Roles of Mast Cells in Obesity and Diabetes: Lessons from Experimental Animals and Humans

Thymic expression of insulin-related genes in an animal model of autoimmune type 1 diabetes

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The BB/Wor Rat and the Balance Hypothesis of Autoimmunity

Cited by 52 publications

References 44 publications

Foxp3+CD25+CD4+ natural regulatory T cells in dominant self‐tolerance and autoimmune disease

Foxp3+CD25+CD4+ natural regulatory T cells in dominant self‐tolerance and autoimmune disease

Different Roles of Mast Cells in Obesity and Diabetes: Lessons from Experimental Animals and Humans

Thymic expression of insulin-related genes in an animal model of autoimmune type 1 diabetes

Contact Info

Product

Resources

About

Foxp3⁺CD25⁺CD4⁺ natural regulatory T cells in dominant self‐tolerance and autoimmune disease

Foxp3⁺CD25⁺CD4⁺ natural regulatory T cells in dominant self‐tolerance and autoimmune disease