What it is
Follicular helper T (TFH) cells are well known for their role in supporting B cell responses. The authors identify a critical, B cell-independent function for TFH cells: sustaining regulatory T (Treg) cells within gut-associated lymphoid tissues (GALT). TFH cells produce interleukin-2 (IL-2) at the border between T cell and B cell zones and within interfollicular regions, and this localized IL-2 is required to maintain Treg cell homeostasis in GALT and to restrain the expansion of pathogenic effector T cells. Mice selectively lacking IL-2-producing TFH cells develop colitis and fatal inflammation across multiple organs, driven by impaired Treg cell responses in GALT and uncontrolled effector T cell activation. Broad-spectrum antibiotic treatment alleviates both the intestinal and the extraintestinal disease, indicating that loss of tolerance to antigens derived from commensal microbes is a key driver. The authors define a spatially restricted, TFH cell-derived IL-2 niche critical for Treg cell stability in GALT, and an unexpected immunoregulatory role for TFH cells in maintaining gastrointestinal tolerance beyond helping B cells.
Why it matters
In mice, IL-2 from follicular helper T cells sustained gut lymphoid regulatory T cells; mice lacking these IL-2 makers developed colitis and fatal multiorgan inflammation. TFH cells are known for supporting B cell responses. Here they produce IL-2 at the T cell-B cell border and between follicles in gut-associated lymphoid tissue, where it maintains regulatory T cells and restrains pathogenic effector T cells, and broad-spectrum antibiotics eased the disease, pointing to lost tolerance of antigens from commensal microbes as a key driver.
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Filed underT-cell and B-cell Immunology, Psoriasis: Treatment and Pathogenesis, IL-33, ST2, and ILC Pathways