Wingender Lab.

Innate-like T Cells

OVERVIEW

The immune system is commonly divided into innate and adaptive immune system. However, innate T cells bridge these two branches, as they share features with innate NK cells and of adaptive memory T cells. The most frequent and arguably the most important innate T cells are invariant Natural Killer (iNKT) cells and mucosal NKT (mNKT or MAIT) cells. Both cell types are very potent and important effector cells in a variety of immune responses. Furthermore, basically, all iNKT and mNKT cells in every human being express an almost identical antigen receptor and respond to the same antigens in a similar fashion. Therefore, their therapeutic potential is immense as one effective treatment could, in theory, be applied to every human. However, many important aspects of iNKT and mNKT cell biology have not been uncovered. Furthermore, the potential of innate T cells for therapeutic applications for a chronic inflammatory disease has not been explored so far.

RESEARCH INTERESTS
Innate T cells:

Gerhard Wingender Şekil 2The most frequent and arguably the most important innate T cells are invariant Natural Killer (iNKT) cells and mucosal NKT (mNKT or MAIT) cells, which share several unique features:

(1) both cell types use a canonical TCR α-chain, Vα14 (mouse) or Vα24 (human) for iNKT cells and Vα19 (mouse) and Vα7.2 (human) for mNKT cells;

(2) this semi-invariant TCR recognizes antigens presented by a non-polymorphic MHC molecule, CD1d for iNKT cells and MR1 for mNKT cells;

(3) the antigens presented are derived largely from bacterial products, glycosphingolipid, like αGalCer, for iNKT cells and Vitamin B metabolites for mNKT cells;

(4) both types of innate T cells rapidly exert effector functions following stimulation, and by the production of copious amounts of cytokines they can impact a large variety of immune reactions; and therefore

(5) both, iNKT and mNKT cells, have been shown to be important effector cells in anti-microbial as well as autoimmune responses.

Basically, all iNKT and mNKT cells in every human being express a canonical TCR and respond to the same antigens in a similar fashion. Therefore, the therapeutic potential of these innate T cells is immense as one effective treatment could, in theory, be applied to every human.

ONGOING PROJECTS

1) The role of iNKT cells in the lung: iNKT cells play a potent, but surprisingly dichotomous role in lung inflammation: Whereas, following lung infections their Th1 response is protective, during allergic responses, like asthma, their Th2 response is deleterious. We study both types of lung inflammation side-by-side to understand how the initial iNKT cell response in the lung is regulated. As an experimental model, infection with Streptococcus pneumonia and an allergen-induced airway hypersensitivity model are used. Uncovering key regulatory mechanisms in directing iNKT cell responses in the lung will provide novel drug candidates for therapeutic applications.

Gerhard Wingender Şekil

2) Therapeutic potential of NKT10 cells: We recently have discovered a novel subset of iNKT cells with potent regulatory functions, due in part to their production of IL-10. These NKT10 cells are protective during autoimmune responses in the brain and the adipose tissue. We are studying the underlying mechanisms of the regulatory function of NKT10 cells in vivo in more detail. Furthermore, in preclinical studies in humanized mice, we will test the therapeutic potential of NKT10 cells in animal models of multiple sclerosis and obesity. This will be done by targeting iNKT cells in vivo and with in vitro generated NKT10 cells for cell therapy.

3) The role of mNKT cells in autoimmune diseases: Similar to iNKT cells, mNKT cells have been implicated in some bacterial infections and autoimmune responses. However, less is known about the importance of mNKT cells in various autoimmune diseases and about the underlying mechanisms than for iNKT cells. In close collaboration with clinical researchers at DEU, we will investigate these aspects for humans with a special focus on neurological and metabolic autoimmune diseases. Animal models will be employed to elucidate the underlying mechanisms.