The role of CD18 and regulatory T cells in skin inflammation (B11)

• Subject Area: Immunology ; Dermatology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 246807620

β2-integrins play important roles for cell-cell communication between leukocytes and for the extravasation of leukocytes from blood into inflamed tissues, but the relevance of β2-integrins for the function of specific leukocyte populations is as yet unknown. Grabbe and Bopp (TP B11) generated mice with a Treg-specific deletion of CD18, the common β chain of all β2-integrins (Itgb2fl/flFoxp3-Cre), which spontaneously generated severe skin inflammation and systemic immune activation including spontaneous inflammation in lungs and colon, and also developed lymphproliferation, produced antinuclear antibodies and antibodies against epidermal proteins. Surprisingly, immune responses in these mice were heavily skewed towards Th2 type immunity, indicating that impaired Treg cell function may play an important role in the pathophysiology of atopic diseases. In the coming funding period, the contribution of β2-integrins for Th2 type immune responses will be assessed in detail using bulk and scRNA Seq analysis, visualization of the immune synapse and in vivo disease models. Moreover, Treg cell function as well as the function of β2-integrins and other adhesion molecules will be tested in patients with atopic diseases. Key collaborations are/will be established with TP B03 (Mahnke – in vivo models), TP (B04 Samstag – assessment of LFA-1 within immune synapses), C04 Hadashik/Enk – comparison with scurfy mice) and C11N (Roers – connection between NLRP1 and β2-integrin function in atopy and FLG/TMEM79 deficient mice).

• DFG Programme: CRC/Transregios
• Subproject of: TRR 156: The skin as sensor and effector orchestrating local and systemic immunity
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Project Heads: Professor Dr. Tobias Bopp; Professor Dr. Stephan Grabbe