Kidney-Treg · Characterisation and impact of kidney-resident Tregs in kidney physiology and pathologies

Characterisation and impact of kidney-resident Tregs in kidney physiology and pathologies

Regulatory T cells (Tregs) are a subtype of T cells exerting immunosuppressive functions that are vital to prevent autoimmunity. Recently, tissue-resident Tregs have been proposed to be distinct from the generic Tregs in circulation. Such Treg subtypes have already been identified in the gut, muscle and adipose tissue. Beyond the classical immunosuppressive function of Tregs, tissue-resident Tregs also modulate non-immunological process in the tissue. For example, muscle Tregs promote tissue repair and adipose tissue Tregs contribute to maintain insulin sensitivity. Apart from these notable exceptions, our knowledge on tissue-resident Tregs is severely limited. The aims of this project are to characterize Tregs located in the selected tissues and to expand up these tissue resident Treg populations to evaluate their specific impact in the physiology and pathology of these tissues. Previous studies strongly support a role of Tregs for protection from injury and promotion of tissue repair in kidney diseases and highlight the exciting potential of therapies harnessing Tregs in these pathologies. However, a key limitation of these studies, is the systemic nature of the Treg manipulation. Previous works looking at Treg function in this organ are based on a systemic depletion, which cause systemic inflammation, or on systemic supplementation in Tregs isolated from blood or lymphoid organs. Without experiments that distinguish between the function of kidney-resident Tregs and systemic Tregs it remains unknown as to whether the key function resides in peripheral impacts, e.g., reducing priming in the draining lymph nodes, or in tissue-based impacts. Formal analysis of function of Tregs in the kidney requires a new approach, where kidney-Tregs are specifically targeted without impacting the peripheral population. The recent Covid 19 pandemic has highlighted the need for a deep understanding of lung immunity. The lung is in contact daily with many opportunistic pathogens. Upon pathogen invasion, the lung elicits an immune response which leads to the clearance of the pathogens. However, in some individuals, an exacerbated production of proinflammatory cytokines, chemokines, and reactive oxygen species can occur, damaging the lung tissue and affecting breathing. Animal studies demonstrated that more Tregs positively correlates with reduced severity of lung inflammation and that therapeutic transfer of Tregs can revert airway inflammation and tissue damages. These studies provide compelling evidence of Tregs involvement in lung immunity that could be harnessed to potentiate tissue repair. In this study, we investigate the potential of local Tregs expansion in the lung to dampen local inflammation and promote tissue repair following acute viral infection, without affecting the systemic immune responses established in the draining lymph nodes.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз