RESEARCH

ANTIGEN PRESENTING CELLS

obrazek3The fundamental aspect of the immune system is the ability to discriminate between harmless non-self and harmful intruders or self-derived structures and their altered pathogenic counterparts. While T-cells are the essential effector cells responsible for the clearance of pathogens or tolerance to commensals and self-derived structures, the antigen presenting cells and the crosstalk between them and T-cells is the fate-decision point of the immune response. Professional antigen presenting cells of various tissues, ontogenetic origins and physiologic roles share the unique capacity to obtain, process and present the antigen in the context of MHCII to CD4+ T-cells. They are efficiently initiating, polarizing or blocking the T-cell responses. We are especially interested in the role of “non-classical” MHCII positive antigen presenting cells such as epithelial cells or innate lymphoid cells in the regulation of adaptive immunity. We believe that the improved understanding of these immune pathways will lead to more efficiently targeted therapies in chronic diseases with dysregulated tissue homeostasis caused by pathogens or autoimmunity.


MHCII Positive Innate Lymphoid Cells

The important role of innate lymphoid cells (ILCs) is the prompt regulation of immune response, homeostasis and epithelial barrier function by rapid release of cytokines. Strikingly, recent studies described several subsets of ILCs capable of MHCII expression and antigen presentation. Furthermore these cells are able to utilize their antigen presenting capacity to regulate adaptive immune responses. We are studying processes used by MHCII+ ILCs to acquire antigens, present them and thus shape T-cell responses both in steady-state and in conditions perturbed by pathogen infection or autoimmunity.

Aire positive innate lymphoid type 3 like cells acquired antigens derived from Candida albicans. Cell nucleus - DAPI (blue), Aire (green), Candida albicans (red).


Medullary thymic epithelial cells

obrazekMedullary thymic epithelial cells (mTECs) regulate thymic development of T-cells and prevents autoimmunity, caused by the recognition of self-antigens in immune periphery. This is achieved by the ability of mTECs to produce almost entire host’s coding genome and to present it as antigens on their MHC molecules to developing T-cells. The self-reactive T-cell clones are effectively eliminated or converted to T-regulatory cells. Antigens expressed by mTECs can be handed over to other antigen presenting cells in a coordinated manner. We are interested in mechanism regulating mTECs ability to orchestrate intrathymic antigen transfer and in cooperation of distinct thymic antigen presenting cells in enforcing immune tolerance.


Intestinal epithelial cells

Intestinal epithelial cells (IECs) delineate the intestinal lumen and play a major role in the digestive process. Thus they form a first line of barrier separating body from the intestinal lumen full of bacteria. Furthermore they execute a crucial part as effectors in the innate immune response by secreting various antimicrobial products. However their capacity to initialize and regulate adaptive immune responses is only beginning to be uncovered. Recently, the ability of IECs to express MHCII molecules was recognized as a major regulator of intestinal immune responses. We are interested in mechanisms that induce the expression of MHCII on IECs as well as their capacity to use MHCII to present antigens and thus shape T-cell responses to intestinal (patho)bionts. We are also exploring molecular mechanisms employed by IECs to aquire antigens for presentations on MHCII molecules.


FUNDING

We are thankful for support of our research:

uniCharles University PRIMUS program

GACR-EN_CMYK Czech Science Fundation Junior START program