Exploring physiological impacts for bioactive lipids on immune responses in aging lung

Supervisors: Dr Chengcan Yao, Prof Adriano G RossiDr You Zhou

Project description:

Aging is a series of processes with time-dependent deteriorative functional changes of organs, leading to a progressive disability of the organism in response to both internal and environmental stresses. Senescence-associated changes of immune responses in the respiratory tract play important roles in dysfunction of ‘normal’ aging lung and the genesis of chronic lung diseases such as chronic obstructive pulmonary disease and cancer. With increased life expectancy, a thoroughly advanced understanding how the respiratory system undergoes physiological and immunological changes with age is needed for the success of public health programmes.

Bioactive lipid mediators play critical roles in maintaining body homeostasis and have divergent effects in response to internal (e.g. age-relate genetic alterations) and external (e.g. life style, smoking, exposure to pollution, etc) influences. Prostaglandins (PGs), especially PGE2, are important lipid mediators which are produced in homeostatic tissues at physiological levels. PGE2 exerts its biological actions through binding to its receptors termed EP1-EP4. While engagement of EP2 and EP4 results in activation of cAMP signalling, EP1 and EP3 couple to activate calcium signalling and down-regulate cAMP signalling, respectively. PGE2 regulates many physiological processes, e.g. it mediates the pain response (via EP2), fever generation (via EP3) and stress behaviour (via EP1), fertilization facilitation (via EP2), bone formation (via EP4) and other important processes. We and others have recently defined that PGE2 has profound impact on regulating both tissue resident and systemic immune responses. For example, PGE2 regulates effector T cell responses to environmental antigen stimulation and gut innate immune homeostasis (refs 1,2). During the process of aging, levels of PGE2 are altered in most tissues including the lung, which is inversely correlated with the progressing dysfunction of tissue homeostasis and dysfunction of organs.

In this PhD project we propose to study how bioactive lipid mediators are changed and how these changes modulate lung immune responses by focusing on adaptive and innate lymphocytes during physiological aging. We will employ cutting-edge immunological, physiological and genetic approaches to investigate the link between the lipid pathways and aging-associated lung immune dysfunction. We will also integrate the analysis of genome-wide gene expression data (e.g. microarray or RNA-sequence) and lipidomic data (e.g. arachidonic acid metabolites) to address the links among lipid mediators, transcriptomic networks and lung immune phenotypic traits in the normal aging process. Success in this project will help us to improve the understanding of the biology for immunological senescence, to ameliorate the negative consequences of advanced age, and to promote human health.

In terms of training, student involved in this project will gain a wide range of knowledge and skills in molecular biology, cellular biology and immunology, lung physiology and systemic biology.  Student will also learn skills for statistical analysis of genomic and lipidomic data. Furthermore, students will receive excellent training on in vivo skills for working with rodent animals and on other skills for researcher development. The student will be assessed and benefit from the expertise in the well established postgraduate committee embedded within the MRC Centre for Inflammation Research.


  1. Robb CT, McSorley HJ, Lee J, Aoki T, Yu C, Crittenden S, Astier AL, Felton J, Parkinson N, Ayele A, Breyer RM, SM, Narumiya S, Rossi AG, Howie SE, Guttman-Yassky E, Weller RB, Yao C. (2017) Prostaglandin E2 stimulates adaptive IL-22 production and promotes atopic dermatitis. J Allergy Clin Immunol. DOI: http://dx.doi.org/ 10.1016/ j.jaci.2017.04.045.
  2. Duffin R, O’Connor RA, Crittenden S, Forster T, Yu C, Zheng X, Smyth D, Robb CT, Rossi F, Skouras C, Tang S, Richards J, Pellicoro A, Weller RB, Breyer RM, Mole DJ, Iredale JP, Anderton SM, Narumiya S, Maizels RM, Ghazal P, Howie SE, Rossi AG, Yao C. (2016) Prostaglandin E2 constrains systemic inflammation through an innate lymphoid cell-IL-22 axis. Science. 351, 1333–1338.
  3. Yao C, Sakata D, Esaki Y, Li Y, Matsuoka T, Kuroiwa K, Sugimoto Y, Narumiya, S. (2009) Prostaglandin E2-EP4 signaling promotes immune inflammation through TH1 cell differentiation and TH17 cell expansion. Nat Med. 15, 633–640.