The Integrin LFA-1 Controls T Follicular Helper Cell Generation and Maintenance
| Autor: | Michael Elliot, Mifong Tam, Ghislaine Fontes, Mary M. Stevenson, Alexandre P. Meli, Stuart G. Tangye, André Ballesteros-Tato, Scott A Leddon, Irah L. King, Danielle T. Avery, Deborah J. Fowell, James H. Miller |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cellular differentiation Immunology Integrin Cell chemical and pharmacologic phenomena Biology Lymphocyte Activation Article Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Humans Immunology and Allergy Lymphocyte function-associated antigen 1 Cells Cultured Effector Germinal center Cell Differentiation T-Lymphocytes Helper-Inducer Germinal Center Acquired immune system Lymphocyte Function-Associated Antigen-1 Immunity Humoral Cell biology Mice Inbred C57BL 030104 developmental biology Infectious Diseases medicine.anatomical_structure Humoral immunity Proto-Oncogene Proteins c-bcl-6 biology.protein 030215 immunology |
| Zdroj: | Immunity. 45:831-846 |
| ISSN: | 1074-7613 |
| Popis: | T follicular helper (Tfh) cells are a CD4+ T cell subset critical for long-lived humoral immunity. We hypothesized that integrins play a decisive role in Tfh cell biology. Here we show that Tfh cells expressed a highly active form of leukocyte function-associated antigen-1 (LFA-1) that was required for their survival within the germinal center niche. In addition, LFA-1 promoted expression of Bcl-6, a transcriptional repressor critical for Tfh cell differentiation, and inhibition of LFA-1 abolished Tfh cell generation and prevented protective humoral immunity to intestinal helminth infection. Furthermore, we demonstrated that expression of Talin-1, an adaptor protein that regulates LFA-1 affinity, dictated Tfh versus Th2 effector cell differentiation. Collectively, our results define unique functions for LFA-1 in the Tfh cell effector program and suggest that integrin activity is important in lineage decision-making events in the adaptive immune system. |
| Databáze: | OpenAIRE |
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