Barbara Nikolajczyk, Ph.D

Mechanisms that control inflammation in type 2 diabetes

Projects in the Nikolajczyk lab focus on understanding how immune system cells modulate systemic inflammation in type 2 diabetes (T2D) patients. Inflammation is strongly implicated in the most dire complications of T2D, including cardiovascular disease and stroke. We are focusing on the role immune system cells promote inflammation and/or insulin resistance in T2D patients and in mouse models of obesity-associated insulin resistance.

Project 1: Recent work showed that B cells promote obesity-associated inflammation through two mechanisms. First, B cells from T2D subjects secrete a pro-inflammatory cytokine profile that includes the inability to produce the potent anti-inflammatory cytokine IL-10. Second, B cells support Th17-mediated inflammation through a contact-dependent T2D-associated mechanism. The goal of this work is to identify molecular processes that initiate and mediate these B cell functions in T2D towards identifying novel drug targets for the endocrinology clinic.

Project 2: A second focus of the Nikolajczyk lab is to understand how B cells contribute to T2D inflammation in individuals with and without confounding periodontal disease. Surprisingly, B cells promote periodontal disease in obese/insulin resistant mice, but not in lean mice. These data indicate that mechanisms of periodontal disease pathogenesis are fundamentally different depending on the metabolic status of the host, and suggest similar differences may underlie other T2D co-morbidities that also occur outside the realm of obesity and insulin resistance.

References.

1. Shin H, Zhang Y , Jagannathan M, Hasturk H, Kantarci A, Liu H, Van Dyke TE, Ganley-Leal LM, Nikolajczyk BS. B cells from periodontal disease patients express surface Toll-like receptor 4. J Leukoc Biol. 2009 April; 85(4): 648–655. PMCID:
PMC2718806

2. Jagannathan M, Hasturk H, Liang Y, Shin H, Hetzel JT, Kantarci A, Rubin D, McDonnell ME, Van Dyke TE, Ganley-Leal LM, Nikolajczyk BS. TLR Cross-Talk Specifically Regulates Cytokine Production by B Cells from Chronic Inflammatory Disease Patients. J Immunol. 2009; 183(11): 7461–7470. PMCID: PMC2851147

3. Jagannathan-Bogdan M, McDonnell ME, Shin H, Rehman Q, Hasturk H, Apovian CM, Nikolajczyk BS. Elevated Proinflammatory Cytokine Production by a Skewed T Cell Compartment Requires Monocytes and Promotes Inflammation in Type 2 Diabetes. J Immunol. 2011; 186(2): 1162–1172. PMCID: PMC3089774

4. Nikolajczyk BS. B cells as under-appreciated mediators of non-auto-immune inflammatory disease. Cytokine. 2010 June; 50(3): 234–242. PMCID: PMC2917985

5. Jagannathan M, McDonnell M, Liang Y, Hasturk H, Hetzel J, Rubin D, Kantarci A, Van Dyke TE, Ganley-Leal LM, Nikolajczyk BS. Toll-like receptors regulate B cell cytokine production in patients with diabetes. Diabetologia. 2010;53:1461-71. PMCID:
PMC2895399

6. DeFuria J, Belkina AC, Jagannathan-Bogdan M, Snyder-Cappione J, Carr JD, Nersesova YR, Markham D, Strissel KJ, Watkins AA, Zhu M, Allen J, Bouchard J, Toraldo G, Jasuja R, Obin MS, McDonnell ME, Apovian C, Denis GV, Nikolajczyk BS. B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile. Proc Natl Acad Sci U S A. 2013; 110(13): 5133–5138. PMCID: PMC3612635

7. Belkina AC, Nikolajczyk BS, Denis GV. BET protein function is required for inflammation: Brd2 genetic disruption and BET inhibitor JQ1 impair mouse macrophage inflammatory responses. J Immunol. 2013; 190: 3670–3678. PMCID:PMC3608815

8. Zhu M, Nikolajczyk BS. Immune cells link obesity-associated type 2 diabetes and periodontitis. Dent Res. 2014 Apr;93(4):346-52. PMCID:PMC3957341 [Available on 2015/4/1]

 

 

 

 

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