Mark Wilson group

Regulation of T helper 2 (Th2) cell development and function during helminth infection and allergy

Approximately ¼ of the world’s population are infected with a parasitic helminth (Schistosome, roundworm, hookworm or whipworm). Similarly, over 150 million people currently suffer from a form of allergic disease. Interestingly, these diseases tend not to overlap (Wilson et al, 2005; Wilson et al, 2004). The aim of our lab is to understand how the immune system responds to parasitic helminth infections and likewise how the immune system responds to allergens. These two areas of interest are not random. Following infection by parasitic helminth’s, or exposure to various airborne or food allergens, a common CD4+ T helper 2 (Th2) response develops, uniting these two areas of study.

In the case of helminth infections, mounting an efficient and robust Th2 response is desired, to mobilize innate immune cells and invoke appropriate tissue responses to kill and clear the parasitic infection. However, mounting a robust Th2 response following contact with harmless allergens is undesired and can lead to many allergic symptoms including allergic asthma, rhinitis and food allergies. In the lab we use experimental models of helminth infection and allergy to ask fundamental questions relating to Th2 immunobiology.

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Goblet cell hyperplasia in the allergic lung as a result of CD4 Th2-mediated airway inflammation. (AB-PAS stained lung, Wilson and Elnekave et al, 2007.)

Th2 responses

Th2 responses

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Understanding the molecular and immunological mechanisms that regulate Th2 responses may allow us to boost Th2 cells to increase immunity to combat helminths or to suppress Th2 responses to prevent allergic diseases.

We are currently asking several general questions relating to Th2 immunobiology, employing functional in vivo models of helminth infection and allergy:

  1. How do micro ribonucleic acids (miRNA’s) manipulate and modify Th2 cell development and effector function? How do the molecular signatures of Th2 cells differ from that of Th1, Th17 and ‘Th9’ cells?
  2. How pliable or plastic are Th2 cells in vivo and how do host protective Th2 cells mature? What are the dynamics of allergen-reactive Th2 cells in diseased tissues?
  3. Can we use immuno-modulators, complimenting vaccinology, to combat helminth infection? Can different classes of immuno-modulators be used to attenuate allergic reactions? (Wilson et al, 2008)

The consequences of dysregulated immune responses are often more damaging than the initial insult (Wilson and Wynn, 2009). For example, if the host responds too vigorously following infection with an excessive immune response, local tissue damage can cause more damage than good- referred to as Immunopathology (Wilson, Mentink-Kane et al, 2007). It is therefore critical that during chronic infection (Wilson, Elnekave et al, 2007) or prolonged exposure to environmental antigens (Wilson et al, 2010) the immune system employs immuno-regulatory mechanisms to calibrate the immune response and prevent immunopathology, while still responding to the pathogen.

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Th2-dependent intestinal granuloma following infection with Schistosoma mansoni. (Mason's Trichrome stained small intestine)

This immunological balance between host protection and immunopathology is at the heart of many of our studies. Investigating cell intrinsic (miRNA), autocrine (Th2->Th2), paracrine (Th1,17,9->Th2) and population level regulation of Th2 cell development, may provide such knowledge to manipulate these important immune cells.

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Chemical or antigen induced pulmonary fibrosis, mediated by IL-17A. (Mason's Trichrome stained lung, Wilson et al, 2010.)

Selected publications

Wilson group

Dr Mark Wilson

Mark Wilson
mwilson@nimr.mrc.ac.uk

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