Evento
Human STAT5 Deficiency Results in an Increase of Follicular T Cells Leading to Expanded Germinal Center B Cells and Autoimmunity
Tipo del evento:
Reunión
Nombre del evento:
Annual Meeting: Immune Deficiency & Dysregulation North American Conference
Fecha del evento:
04/2019
Institución Organizadora:
Clinical Immunology Society;
Título de la revista:
Journal of Clinical Immunology
Editorial:
Springer
ISSN:
1573-2592
Idioma:
Inglés
Clasificación temática:
Resumen
Introduction: The fate of effector T cells is strongly dependent on the expression of Bcl-6 or Blimp-1, which are inhibited reciprocally through a complex signaling pathway. Several studies have shown that Bcl-6 is a key transcription factor for differentiation towards the follicular helper T cells (Tfh) lineage able to collaborate with B lymphocytes (BL). On the contrary, the transcription factor Blimp-1 is highly expressed in T lymphocytes Th1, Th2 and Treg, thus regulating the differentiation towards Tfh. Materials and methods: whole fresh blood and peripheral mononuclear cells from a patientwith homozygous mutation in STAT5b were analysed by flow cytometry. Analysis of cTfh (CD4+CD45RA-CXCR5+), cTfh1 (CXCR3+), cTfh17 (CCR6+), cTfh2 (CXCR3-CCR6-), naïve BL (LB IgM+IgD+CD27-), memory (MBL) (LB IgM+ IgD- CD27+), switched (MBL-Sw) (IgD-IgM-) andplasmablast (PBC) (CD27+CD38++) cells was performed. Immunoglobulins were measured in serum. Results: the patient with STAT5b deficiency showed increased values of cTfh (38%) (Healthy donors p10-p90: 7,9-17,8 %) that presented an activated phenotype (ICOS+ and PD-1+) with a skewed to a Th17 profile (CCR6+), consistent with her hipergammaglobulinemia and the marked and sustained increase in the switched MBL and PBC subpopulations in peripheral blood over the years. Discusion: This immunological phenotype described in the patient with STAT5b deficiency could explain in part the pathophysiology of the autoimmune disorders. This patient (as well as the other two patients withmutations in STAT5b previously described by our group), have had chronichypergammaglobulinemia, autoantibodies and consequently autoimmune processes (psoriasis, hypothyroidism, eczema, alopecia and celiac disease, among others).We believe that the link between this clinical symptomatology and the molecular defect relies in the fact that the absence of STAT5b promotes a greater expression of Bcl-6, which generates a bias towards the production of cTfh cells, that give rise to a greater activation of LB, generation of LBMand plasma cells (dysregulation in the CG), events thatmanifest as hypergammaglobulinemia and autoimmunity. In summary, we provide promising evidence of the mechanisms that lead to autoimmunity in thistype of patients that could also be a consequence of the defect in the regulation of GC, highlighting the crucial role of STAT5b in the humoral immune response and maintenance of the tolerance of the immune system.
Palabras clave:
STAT5b
,
Follicular T cells
,
Germinal center
,
Primary immunodeficiencies
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Eventos(IBYME)
Eventos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Eventos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Eventos(IMIPP)
Eventos de INSTITUTO MULTIDISCIPLINARIO DE INVESTIGACIONES EN PATOLOGIAS PEDIATRICAS
Eventos de INSTITUTO MULTIDISCIPLINARIO DE INVESTIGACIONES EN PATOLOGIAS PEDIATRICAS
Citación
Human STAT5 Deficiency Results in an Increase of Follicular T Cells Leading to Expanded Germinal Center B Cells and Autoimmunity; Annual Meeting: Immune Deficiency & Dysregulation North American Conference; Atlanta; Estados Unidos; 2019; 83-84
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