Interventional Immunology in Neonatal Diseases

Interventional Immunology in Neonatal Diseases Research Group

Research Group Heads

The Nold Laboratory has its roots in basic science; however, these days our main interest lies in harnessing our expertise in immunology to explore the molecular mechanisms of several poorly understood and currently largely untreatable diseases that affect the tiniest patients of any hospital, namely babies born prematurely. These diseases include bronchopulmonary dysplasia (BPD) that severely compromises lung function and entails pulmonary arterial hypertension (PAH), which in turn often causes right heart failure; intracranial haemorrhage (ICH) whose survivors commonly require extensive special education; and necrotising enterocolitis (NEC), a disease of the intestine that carries up to 70 per cent mortality. Our primary aim is rapid translation of our findings into clinical medicine, as best exemplified by a planned clinical trial that is based on one of our discoveries (see paper #1 below) and that may establish the first safe and effective treatment for BPD.

Our laboratory’s second major focus lies on the new interleukin (IL-)1 family cytokines IL-37 and IL 38. Our revelation of the powerful anti-inflammatory properties of IL-37 (#2 below) and its signalling mechanisms and cell surface receptor (#3 below) has led to a surge of international interest in these previously largely obscure cytokines. Examples of our current work include exploration of the therapeutic potential of IL-37 in paediatric and adult illnesses (#4&5 below), and the characterisation of IL-38 in health and disease, including in systemic lupus erythematosus (SLE), an incurable autoimmune disease that affects women during their childbearing age and their unborn children.

Research Projects

1. Exploring a new frontier: The immune and coagulation systems of the premature infant and their relevance for the risk of the major diseases of prematurity.
Direct clinical relevance: high. Hands-on learning opportunities: Multi-color flow cytometry, protein arrays, cell culture of primary human blood cells.

2. Molecular tracking of the cytokine IL-37 in anti-inflammatory signalling.
Direct clinical relevance: medium/low. Hands-on learning opportunities: Confocal microscopy, molecular engineering (cloning), cell culture of primary human blood cells and cell lines.

3. Novel anti-inflammatory approaches for currently untreatable diseases of the preterm baby: IL-1Ra and IL-37 in animal models of bronchopulmonary dysplasia and necrotising enterocolitis.
Direct clinical relevance: high. Hands-on learning opportunities: Various aspects of work with mice, workup of tissues for various downstream applications, flow cytometry, histology, immunohistochemistry, protein detection by ELISA, synchrotron X-ray imaging.

4. Molecular characterisation of regulation and mechanism of action of the anti-inflammatory cytokine interleukin 37.
Direct clinical relevance: medium/low. Hands-on learning opportunities: Culture of primary human blood cells and cell lines, protein detection by ELISA, RNA detection by real-time PCR, flow cytometry, immunohistochemistry.

5. The first in vivo exploration of IL-38.
Direct clinical relevance: medium/low. Hands-on learning opportunities: Various aspects of work with mice, workup of tissues for various downstream applications, flow cytometry, histology, immunohistochemistry, protein detection by ELISA, RNA detection by real-time PCR.

Research Group

  • Steven Chonwerawong, Postdoctoral Scientist
  • Dr Devi Ngo, Postdoctoral Scientist
  • Dr Ina Rudloff, Postdoctoral Scientist
  • Tessa Svinos, Honours Student

Selected publications

  • Nold MF, Mangan NE, Rudloff I, Cho SX, Shariatian N, Samarasinghe TD, Skuza EM, Veldman A, Berger PJ, Nold-Petry, CA: Interleukin 1 receptor antagonist prevents murine bronchopulmonary dysplasia induced by perinatal inflammation and hyperoxia. Proc Natl Acad Sci USA 110 (35):14384-89, August 2013.

  • Nold MF, Nold-Petry CA, Zepp JA, Palmer BE, Bufler P, Dinarello CA: IL-37 is a fundamental inhibitor of innate immunity. Nat Immunol 11(11):1014-22, November 2010.

  • 35. Nold-Petry CA, Lo CY, Rudloff I, Elgass KD, Li S, Gantier MP, Lotz-Havla AS, Gersting SW, Cho SX, Lao JC, Ellisdon AM, Rotter B, Azam T, Mangan NE, Rossello FJ, Whisstock JC, Bufler P, Garlanda C, Mantovani A, Dinarello CA, Nold MF. IL-37 requires the receptors IL-18Ralpha and IL-1R8 (SIGIRR) to carry out its multifaceted anti-inflammatory program upon innate signal transduction. Nat Immunol. 2015 Apr;16(4):354-65

  • 34. Cottle DL, Ursino GM, Ip SC, Jones LK, Ditommaso T, Hacking DF, Mangan NE, Mellett NA, Henley KJ, Sviridov D, Nold-Petry CA, Nold MF, Meikle P, Kile BT, Smyth IM. Fetal inhibition of inflammation improves disease phenotypes in harlequin ichthyosis. Hum Mol Genet. 2015 Jan 15;24(2):436-49

  • 27. McNamee EN, Masterson JC, Jedlicka P, McManus M, Grenz A, Collins CB, Nold MF, Nold-Petry C, Bufler P, Dinarello CA, Rivera-Nieves J. Interleukin 37 expression protects mice from colitis. Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16711-6.