Séminaire CIRI : Dr. Sandrine HENRI & Dr. Mei LI
Date / Heure
Date(s) - 26/11/2020
14 h 00 min - 15 h 30 min
Dr. Sandrine HENRI (Centre d’Immunologie Luminy-Marseille), « Role of dendritic cells in tolerance to self-antigen »
We showed in the past that dermal conventional type 1 dendritic cells (cDC1) were the most efficient for self-antigen cross-presentation to CD8+ T cells. We generated a new mouse model (Xcr1-cre-mTFP1) and studied in more details the immunobiology of cDC1 in vivo and in particular, we showed their importance in tumor immunity and their key role in peripheral tolerance. Indeed, using the K5-mOVA mouse model we showed that impairing MHCII expression by cDC1 caused autoimmune syndromes.
Dr. Mei LI (Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France). “ Dual function of Langerhans cells in skin TSLP-promoted Tfh cell differentiation in mouse atopic dermatitis ”
Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases with increasing prevalence worldwide. It usually occurs early in life, and it often precedes other atopic diseases like asthma in the process called “atopic march”. For a long time, Th2 cell has been believed to play a crucial role in cellular response and humoral response in AD, but accumulating evidences have shown that T follicular helper (Tfh) cell, a critical player in humoral immunity, is associated with disease severity and play an important role in AD pathogenesis. Yet, how Tfh cells are generated and regulated in AD had remained to be investigated. In this study, by employing two experimental AD mouse models, triggered by the overproduction of TSLP in mouse skin through topical application of MC903, or induced by epicutaneous allergen ovalbumin (OVA) sensitization, we demonstrated that TSLP is not only sufficient but also crucial for driving Tfh cell differentiation and germinal center (GC) response in skin-draining lymph nodes. Intriguingly, we further uncovered that epidermal Langerhans cell (LC) exerts the opposite regulation of Tfh as well as Th2 cell differentiation in the two models. In MC903-AD, LC promotes Tfh cell differentiation and GC response, and to a lesser extent contributes to skin Th2 response; but in OVA-AD, LC counteracts Tfh/GC response, limits Th2 skin inflammation, and suppresses the atopic march. Together, these studies revealed the dual functionality of LCs in TSLP-promoted Tfh and Th2 cell differentiation in AD pathogenesis.