Tissue-specific immune cell networks
BBSRC David Phillips Fellow
Mucosal barrier sites pose a particular challenge for the immune system. These barriers, such as the Gastrointestinal (GI) tract and Oral mucosa, are sites of frequent pathogen invasion but also home to diverse commensal microbial communities.
As such, the immune system must be carefully tailored to the tissue microenvironment to limit aberrant responses to commensals while allowing for rapid development of an immune response to protect against the invader. Failure to achieve this has pathological consequences such as the development of inflammatory bowel diseases (Gastrointestinal tract) and Periodontitis (Oral mucosa).
Consequently, specialised immune cell networks have developed to help mediate effective immunological control of these dynamic barrier environments.
Our research programme focuses on understanding how the immune system is tailored to these unique barrier surfaces and how these networks evolve with age. Indeed, to mediate immune homeostasis at the barrier sites of GI tract and oral mucosa, conventional and unconventional immune cells are present which are conditioned by the microenvironment.
Our recent work has examined the development and differentiation of T cells at barrier sites, understanding how barrier-specific cues, in particular the cytokine TGFβ, eeducates T cells about their environment and drives them to adopt certain phenotypic and functional characteristics.
Inflammation at the oral mucosa
In our ongoing work, we are further exploring the immune cell networks present at barrier sites, with a particular focus on the oral mucosa. Indeed, in a collaborative study, we have highlighted the key role of immune dysfunction in the development of Periodontitis, emphasising the strict controls placed on immune cell functioning at the oral barrier. However, a clear picture of the immune homeostatic mechanisms at play at the oral barrier is yet to be elucidated.
To address this, we are undertaking parallel studies in both human and mouse that will allow for an in-depth investigation of this often overlooked mucosal site. Having been awarded a BBSRC David Phillips Fellowship, Dr Konkel aims to mechanistically understand the signals that are required to establish the immunological network present at the oral barrier and delineate how this network changes with age.
This is an important question as advancing age is associated with loss of immune homeostasis at this unique barrier site. Collectively, this work will outline how alterations in the oral immuno-surveillance network contribute to immune dys-regulation and pathological inflammation in the oral cavity.
In addition, we are also exploring the influence of immune cell functioning at the oral barrier on immunity at distal sites, in particular the gastrointestinal tract, and identifying the meditators of this cross-talk.
Collectively, understanding the mechanisms behind immune specialisation at barrier sites will not only allow for a better understanding of barrier immunity in human health and disease, but could also lead to the identification of targets for the rational development of novel therapeutics.