This Research Topic is the second volume in this series, "Community Series in Follicular Helper T Cells in Immunity and Autoimmunity". Please see volume I here.

The field of immunology has seen significant advancements in understanding the role of T follicular helper (Tfh) cells, which are crucial for B cell maturation within germinal centers (GCs). These specialized T cells, upon encountering antigens, upregulate the chemokine receptor CXCR5, allowing them to localize within B cell follicles and initiate the GC response alongside dendritic cells and B cells. Recent studies have identified various Tfh subsets based on chemokine receptor expression and activation molecules, linking their distribution and activation phenotype to clinical outcomes in diseases ranging from autoimmunity to immunodeficiency. Despite these advancements, the differentiation and plasticity of Tfh subsets, their interactions with B cells outside GCs, and the mechanisms influencing their impact on B cell activation remain largely unexplored. Additionally, the role of FOXP3+ regulatory T cells (Tfr) in controlling GC responses and the factors governing their generation and suppression are not well understood. As Tfh and Tfr cells emerge as biomarkers and therapeutic targets in clinical settings, a deeper understanding of their development and function is essential for advancing immune-monitoring and therapy.

This research topic aims to delve into the biology of Tfh cells, exploring how these cells can be targeted to modulate immune responses, either by suppressing unwanted reactions or enhancing immunity. The primary objectives include investigating the lineage specification of Tfh subsets, understanding the molecular and extrinsic signals that govern their development, and elucidating the regulatory roles of Tfr cells in GC responses. By addressing these questions, the research seeks to provide insights that could inform the development of Tfh-based therapeutic strategies and improve clinical outcomes in various diseases.

To gather further insights into the complex roles of Tfh and Tfr cells in immunity and autoimmunity, we welcome articles addressing, but not limited to, the following themes:
- Lineage specification of Tfh subsets and their function
- Molecular control of Tfh development and differentiation
- T-cell extrinsic signals that control Tfh development
- Regulation of GC responses by Tfr cells
- Tfh in infections
- Tfh in vaccine response
- Tfh in antiviral immunity
- Tfh in autoimmune disorders
- Tfh in primary immunodeficiencies
- Tfh in transplantation tolerance
- Tfr in cancer
- Tfr in immune response changes in aging
- Biomarker development and therapeutic targeting of Tfh

Topic Editor Cicalese Maria Pia is associated/works for Vita-Salute University, IRCCS San Raffaele Institute, Milan, Italy and San Raffaele Telethon Institute for Gene Therapy (SR-Tiget); The other Topic Editors declare no competing interests with regard to the Research Topic subject

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Frontiers in Immunology

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