The Role of LFA-1 for the Differentiation and Function of Regulatory T Cells-Lessons Learned from Different Transgenic Mouse Models

• Published in: International journal of molecular sciences Vol. 24; no. 7; p. 6331
• Main Authors: Klaus, Tanja, Wilson, Alicia, Fichter, Michael, Bros, Matthias, Bopp, Tobias, Grabbe, Stephan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.03.2023; MDPI
• Subjects: Analysis; Animal models; Animals; Antigens; Arthritis; Autoantigens; Autoimmune Diseases; Autoimmunity; Bacterial infections; CD11a antigen; CD18 antigen; CD18 Antigens - genetics; CD18 Antigens - metabolism; Cell culture; Cell Differentiation - genetics; Cell signaling; Chemokines; Cytokines; Diabetes; Disease; Genetic engineering; Genotype & phenotype; Homeostasis; Humans; Immune system; Immunological tolerance; Immunoregulation; Integrins; Kinases; Leukocytes; Leukocytosis; LFA-1; LFA-1 antigen; Ligands; Lymphocyte Function-Associated Antigen-1 - genetics; Lymphocyte Function-Associated Antigen-1 - metabolism; Lymphocytes; Lymphocytes T; Maintenance; Mice; Mice, Transgenic; Mutation; Phenotypes; Review; Signs and symptoms; T cell receptors; T cells; T-Lymphocytes, Regulatory - metabolism; Transcription factors; Transgenic mice; transgenic mouse models; Treg; Tumor necrosis factor-TNF; Germany; LFA-1; Treg; transgenic mouse models
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24076331

Regulatory T cells (Treg) are essential for the maintenance of peripheral tolerance. Treg dysfunction results in diverse inflammatory and autoimmune diseases with life-threatening consequences. β -integrins (CD11a-d/CD18) play important roles in the migration of leukocytes into inflamed tissues and cell signaling. Of all β -integrins, T cells, including Treg, only express CD11a/CD18, termed lymphocyte function-associated antigen 1 (LFA-1), on their surface. In humans, loss-of-function mutations in the common subunit CD18 result in leukocyte adhesion deficiency type-1 (LAD-1). Clinical symptoms vary depending on the extent of residual β -integrin function, and patients may experience leukocytosis and recurrent infections. Some patients can develop autoimmune diseases, but the immune processes underlying the paradoxical situation of immune deficiency and autoimmunity have been scarcely investigated. To understand this complex phenotype, different transgenic mouse strains with a constitutive knockout of β -integrins have been established. However, since a constitutive knockout affects all leukocytes and may limit the validity of studies focusing on their cell type-specific role, we established a Treg-specific CD18-floxed mouse strain. This mini-review aims to delineate the role of LFA-1 for the induction, maintenance, and regulatory function of Treg in vitro and in vivo as deduced from observations using the various β -integrin-deficient mouse models.