title: Lymphopenia and autoimmunity: A double-edged sword.
abstract: Lymphopenia is strongly associated with autoimmune diseases. The molecular mechanisms that link both phenomena are still unclear, but certain key pathways have been described. Central tolerance is as important as peripheral. In the earlier, epithelial and dendritic cells play a crucial role in the selection of clones. In the latter, regulatory T cells (Tregs) rise as inductors of anergy in order to prevent the development of autoimmune pathology. In lymphopenic conditions, T cells develop the process of lymphopenia-induced proliferation (LIP). A complex interaction between the major histocompatibility complex (MHC) and the T cell receptor (TCR) makes this process possible. Furthermore, IL-7 can act synergistically or in an independent manner to promote LIP. A lack of Transforming Growth Factor-β (TGF-β) was recently described as the second hit needed to develop autoimmunity in a lymphopenic microenvironment, given its actions in Tregs and its interaction with CTLA-4. Regarding autoimmune clinical scenarios, lymphopenia is related to both, systemic and organ-specific diseases. Thus, the molecular study of such patients has been limited and needs to be widened to the pathways shown here to be involved in the development of lymphopenia and autoimmunity.
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan 14080, Mexico City, Mexico.
authors.forename: Javier
authors.initials: J
authors.lastname: Merayo-Chalico
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan 14080, Mexico City, Mexico.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rajme-López
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan 14080, Mexico City, Mexico.
authors.forename: Ana
authors.initials: A
authors.lastname: Barrera-Vargas
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan 14080, Mexico City, Mexico.
authors.forename: Jorge
authors.initials: J
authors.lastname: Alcocer-Varela
authors.affiliation: Department of Radiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan 14080, Mexico City, Mexico.
authors.forename: Mariana
authors.initials: M
authors.lastname: Díaz-Zamudio
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan 14080, Mexico City, Mexico. Electronic address: d_gomar@hotmail.com.
authors.forename: Diana
authors.initials: D
authors.lastname: Gómez-Martín
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity; D060908:CTLA-4 Antigen / Q000378:metabolism; D060966:Clonal Selection, Antigen-Mediated; D006706:Homeostasis; D006801:Humans; D007108:Immune Tolerance; D015851:Interleukin-7 / Q000378:metabolism; D008231:Lymphopenia / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D060908:CTLA-4 Antigen; D015851:Interleukin-7; D016212:Transforming Growth Factor beta
keywords: IL-7; Lymphopenia; Systemic lupus erythematosus; T cells