Th Cell Differentiation

T helper cell activation and differentiation to functionally distinct subsets
Selective activation of T helper (Th) cell subsets plays an important role in the pathogenesis of human allergy and inflammatory diseases. Dissecting pathways and regulatory networks leading to the development of Th1 or Th2 cells will be crucial to understand the pathogenesis of allergy and inflammatory diseases. Improved understanding may lead to better strategies for developing diagnostics and effective therapies for these diseases.
 
Cytokines IL-12 and IL-4 selectively regulate the development and differentiation of CD4+ T cell subsets to IFN-γ and IL-2 producing Th1 cells or IL-4 and IL-5 secreting Th2 cells, respectively. Th2 cytokines lead to a series of inflammatory processes characteristic for asthma and other atopic diseases (e.g. production of IgE, mast cell and eosinophil activation). Th1 cells, on the other hand, play a role in the pathogenesis of autoimmune diseases (e.g. type I diabetes). IL4R activation leads to activation of Signal Transducer and Activator of Transcription (STAT) protein 6. STAT6-/- mice are unable to mount a Th2 or an IgE response and are resistant to antigen induced airway inflammation and airway hyperresponsiveness, emphasizing the key role IL4R/STAT6 signalling in asthma.

We were among the first to report functionally distinct Th1 and Th2 subsets in human. During the past few years our studies have focused on signaling and transcriptional regulation of lymphocyte activation and differentiation.
 
Applying a holistic approach to identify genes involved in the process we have profiled gene expression during Th cell activation and differentiation both in human and in mouse. Importantly, our recent data indicate substantial differences in the regulation of gene expression during human Th cell differentiation when compared to that in mouse Th cells.
 
Our recent results have led to novel hypotheses on the key factors involved in human Th cell differentiation. We are currently focusing at elucidating the function of the novel genes and pathways identified in our studies with primary human CD4+ T cells. Detailed analysis of upstream T cell Receptor (TCR)/key cytokine receptor induced signaling pathways and regulatory circuits includes repeated rounds of mathematical modelling and experimental verification. In parallel, the signalling and transcriptional protein complexes are analysed with state-of-the-art proteomics, mass spectrometry and cell imaging techniques to build a model of T cell activation and differentiation.
 
Integrating quantitative data on T cell activation and differentiation will increase our understanding of these processes central for human health and disease and provide novel insights into new therapeutic interventions.

Riitta Lahesmaa, M.D., Ph.D., Professor, Group leader

Kanury Rao, Ph.D., Visiting Professor
Brigitta Stockinger, Ph.D., Visiting Professor
Robert Moulder, Ph.D., Senior Scientist
Juha Pursiheimo, Ph.D., Senior Scientist
Omid Rasool, Ph.D., Adjunct Professor , Senior Scientist

Laura Elo-Uhlgren, Ph.D., Postdoctoral Fellow
Riikka Lund, Ph.D., Postdoctoral Fellow

Helena Ahlfors, M.Sc., Ph.D. Student
Sanna Filen, M.Sc. (on leave), Ph.D. Student
Mirkka Heinonen,  M.Sc., Ph.D. Student
Henna Järvenpää, M.Sc., Ph.D. Student
Juha Korhonen, M.Sc., Ph.D. Student
Minna Kyläniemi, M.Sc., Ph.D. Student
Tapio Lönnberg, M.Sc., Ph.D. Student
Johanna Tahvanainen, M.Sc., Ph.D. Student (on leave)
Soile Tuomela, M.Sc., Ph.D. Student

Marjo Hakkarainen, technician
Sarita Heinonen, technician
Päivi Junni, technician

Marjo Linja, Undergraduate Student
Nelly Rahkonen, Undergraduate Student
Verna Salonen, Undergraduat Student