Generation of autoantibodies is a hallmark of autoimmune diseases. Recent data in humans and mice show that overrepresentation of T follicular helper (Tfh) cells, a CD4+ T cell subset specialized in helping B cells in germinal centers (GCs), is associated with autoimmunity. Yet, the immune mechanisms that cause exaggerated Tfh response in human autoimmune diseases remain largely unknown. Our preliminary studies suggest a common mechanism associated with exaggerated Tfh responses in human autoimmune disease. We identified two candidate factors derived from antigen-presenting cells promoting Tfh responses. Altered Tfh response in autoimmune diseases might be also associated with dysregulated of T follicular regulatory (Tfr) cells that originate from thymus-derived regulatory T cells (Tregs). In this Collaborative Project, we hypothesize that Altered APCs promotes Tfh response while suppressing Tfr response thereby contributing to the pathogenesis of human autoimmune diseases. We will share our established methods for the studies of human Tfh cells to other Centers, so that newly diagnosed untreated patients with a broad range of autoimmune diseases can be analyzed across the Centers.
The specific aims are AIM 1: To determine the alteration in Tfh cell subsets in blood in autoimmune diseases.
AIM 2 : To determine the alteration in Tfh cells and CD11c+ APCs in inflammatory tissues in autoimmune diseases.
AIM 3 : To determine whether APCs in inflammatory tissues are capable of inducing naive and memory CD4+ T cells to differentiate into Tfh cells, and AIM 4: To determine whether and how Tfr response is altered in autoimmune diseases. In conclusion, we might be able to reveal immunological pathways that cause altered Tfh/GC response shared by different autoimmune diseases as well as unique one to each disease.

Public Health Relevance

Autoimmune patients, especially with SLE, continue to have unmet medical needs, necessitating in-depth studies enabling increased understanding of disease pathophysiology and identification of novel therapeutic targets. Our long-term goal is to discover novel target(s) for treatment/prevention of human autoimmune diseases by elucidating the immunological mechanisms associate with dysregulated Tfh/GC responses.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1)
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Baylor Research Institute
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Cepika, Alma-Martina; Banchereau, Romain; Segura, Elodie et al. (2017) A multidimensional blood stimulation assay reveals immune alterations underlying systemic juvenile idiopathic arthritis. J Exp Med 214:3449-3466
Banchereau, Romain; Cepika, Alma-Martina; Banchereau, Jacques et al. (2017) Understanding Human Autoimmunity and Autoinflammation Through Transcriptomics. Annu Rev Immunol 35:337-370
Schmitt, Nathalie; Liu, Yang; Bentebibel, Salah-Eddine et al. (2016) Molecular Mechanisms Regulating T Helper 1 versus T Follicular Helper Cell Differentiation in Humans. Cell Rep 16:1082-1095
Blanco, Patrick; Ueno, Hideki; Schmitt, Nathalie (2016) T follicular helper (Tfh) cells in lupus: Activation and involvement in SLE pathogenesis. Eur J Immunol 46:281-90
Caielli, Simone; Athale, Shruti; Domic, Bojana et al. (2016) Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus. J Exp Med 213:697-713
Banchereau, Romain; Hong, Seunghee; Cantarel, Brandi et al. (2016) Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients. Cell 165:551-65
Turner, Jacob A; Bolen, Christopher R; Blankenship, Derek M (2015) Quantitative gene set analysis generalized for repeated measures, confounder adjustment, and continuous covariates. BMC Bioinformatics 16:272
Jacquemin, Clément; Schmitt, Nathalie; Contin-Bordes, Cécile et al. (2015) OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response. Immunity 42:1159-70
Schmitt, Nathalie (2015) Role of T Follicular Helper cells in Multiple Sclerosis. J Nat Sci 1:e139
Schmitt, Nathalie; Ueno, Hideki (2015) Regulation of human helper T cell subset differentiation by cytokines. Curr Opin Immunol 34:130-6

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