MD/PhD 1 (2015 - 2017) - Immunoregulation of obesity-associated asthma


Obesity is a worldwide increasing health care burden and is strongly associated with chronic systemic inflammation. Since the late 1990’s, various clinical and experimental conditions have shown a strong association between obesity and both the allergic and non-allergic forms of asthma.

Despite the increasing evidences for obesity being a risk factor for the development of asthma, the underlying pathomechanisms are not yet revealed. It becomes more and more obvious that obesity can impact on asthma via different mechanisms: first, asthma and obesity share pathogenetic factors and comorbidities which might act in a synergistic manner; second, the mechanical effect of obesity on the body affects the respiratory function; third, obesity induces a chronic mild systemic inflammation as well as altered secretion of adipokines that have been shown to directly act on lung function, pulmonary composition of inflammatory cells and inflammatory cell functions. Nonetheless, the third point is thought to be the major driving factor. Thus, it could be shown that obesity aggravates the TH2-dependent allergic and eosinophilic asthma and on the other hand impacts on the development of asthma via TH2-independent mechanisms. All this is yet referred to as “obese-asthma” but only few is known about the exact mechanisms involved. The current understanding of this association involves adipokines and their impact on the immune system, altered eosinophil distribution between visceral adipose tissue and asthma, impaired macrophages function and IL-17-producing cells like T-cells and innate-lymphoid cells.

The overarching goal of this project is to delineate the immune mechanisms driving obesity-associated asthma. More specifically, the focus is on the interplay between the visceral adipose tissue and the lung and within this the role of the adipokines and their impact on immune cell function.

To pursue this goal, we will focus on the following specific aims:

  • Aim 1: Establish an experimental mouse model of diet-induced obesity to analyze lung functions and follow changes in immunological cell composition in lung and visceral adipose tissue under basal and allergic conditions.
  • Aim 2: Evaluate the interaction of obesity-induced and allergen-induced alterations in lung mechanics in a chronic asthma model.
  • Aim 3: Dissect the role of the adipokines and adipokine receptors in immune cells in lung and visceral adipose tissue.