Laboratory of Innate Immune Recognition
The evolutionary ancient innate immune system is composed of migrating and tissue-resident innate lymphocytes and myeloid cells. It forms a potent barrier against infections and tumors. As most species exclusively rely on the innate immune system for their defense, its analysis may allow principal insights into primordial ‘Design Principles’ of the immune system. The importance of innate immunity is further stressed by the finding that efficient adaptive (i.e., B or T cell-mediated) immunity of vertebrates requires a functional innate immune system. Thus, therapeutic manipulation of innate immune cells may provide effective strategies for combatting and preventing infections and tumors.
In the past, immunologists have focused to uncover how immune cells discriminate between innocuous ‘self’ and infectious ‘non-self’. Consequently, the immune system is widely perceived as a network of resting cells that once activated by a pathogen unleashes an attack to eradicate the pathogen by use of an array of cytotoxic and antimicrobial effector molecules. However, recent research into immune cells at mucosal sites has revealed a very different picture. At mucosal surfaces, immune cells are constantly confronted with myriads of foreign antigens. It appears that immune recognition at mucosal interfaces occurs continously and has taken on a different ‘meaning’ in that it promotes tissue homeostasis rather than immune activation. Thus, an intimate and often mutualistic relationship between innate immune cells, the indigenous microbiota and epithelial cells has been established. We have identified the first molecular pathways of how innate lymphocytes within the intestinal mucosa contribute to maintaining tissue homeostasis and to promoting host-microbe mutualism (Sanos, Nat Immunol 2009; Sanos, Immunology 2011; Ganal, Immunity 2012). Interestingly, the transcriptional networks that were uncovered strikingly resemble those reported for the maintenance of epithelial homeostasis in invertebrates (Klose, Curr Opin Immunol 2012). Thus, these lines of research are beginning to reveal previously unappreciated immune functions of innate lymphocytes that apparently consisted in increasing barrier function by promoting epithelial regeneration and by maintaining epithelial homeostasis.
Our current and future research is focused on a molecular understanding of how the innate immune system promotes tissue homeostasis and how host-microbe mutualism is established. In addition, we study development and function of innate lymphocyte lineages (natural killer cells, natural helper cells, lymphoid tissue inducer cells) at mucosal surfaces. It is likely, that such studies will expose primordial functions of the immune system and will identify new targets for the treatment of chronic inflammatory disorders (e.g., Crohn’s disease, ulcerative colitis).