T follicular helper cells, T follicular regulatory cells and autoimmunity

CD4⁺ T follicular helper (Tfh) cells are recognized as a distinct T-cell subset, which provides help for germinal center (GC) formation, B-cell development and affinity maturation, and immunoglobulin class switching, as an indispensable part of adaptive immunity. Tfh cell differentiation depends on various factors including cell-surface molecule interactions, extracellular cytokines and multiple transcription factors, with B-cell lymphoma 6 (Bcl-6) being the master regulator. T follicular regulatory (Tfr) cells are also located in the GC and share phenotypic characteristics with Tfh cells and regulatory T cells, but function as negative regulators of GC responses. Dysregulation of either Tfh or Tfr cells is linked to the pathogenesis of autoimmune diseases such as systemic lupus erythematosus. This review covers the basic Tfh and Tfr biology including their differentiation and function, and their close relationship with autoimmune diseases.

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