A follicular regulatory Innate Lymphoid Cell population impairs interactions between germinal center Tfh and B cells

• Published in: Communications biology Vol. 4; no. 1; p. 563
• Main Authors: O’Connor, Margaret H., Muir, Roshell, Chakhtoura, Marita, Fang, Michael, Moysi, Eirini, Moir, Susan, Carey, Alison J., Terk, Alyssa, Nichols, Carmen N., Metcalf, Talibah, Petrovas, Constantinos, Cameron, Mark J., Tardif, Virginie, Haddad, Elias K.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12-05-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/21; 13/31; 13/51; 14/1; 14/19; 38/1; 38/39; 38/90; 38/91; 631/250/2152/1566/1618; 631/250/2152/2153/1982; 631/250/2504/2506; 82/51; Biology; Biomedical and Life Sciences; Cell interactions; Chronic infection; Follicles; Germinal centers; HIV; Human immunodeficiency virus; Inflammation; Life Sciences; Localization; Lymph nodes; Lymphatic system; Lymphocytes B; Lymphocytes T; Lymphoid cells; Mucosa; Phenotypes; Population; Transcription; Transforming growth factor-b
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-021-02079-0

Innate Lymphoid Cells (ILCs) are immune cells typically found on mucosal surfaces and in secondary lymphoid organs where they regulate the immune response to pathogens. Despite their key role in the immune response, there are still fundamental gaps in our understanding of ILCs. Here we report a human ILC population present in the follicles of tonsils and lymph nodes termed follicular regulatory ILCs (ILC
FR
) that to our knowledge has not been previously identified. ILC
FR
have a distinct phenotype and transcriptional program when compared to other defined ILCs. Surprisingly, ILC
FR
inhibit the ability of follicular helper T (Tfh) cells to provide B cell help. The localization of ILC
FR
to the germinal centers suggests these cells may interfere with germinal center B cell (GC-B) and germinal center Tfh cell (GC-Tfh) interactions through the production of transforming growth factor beta (TGF-β. Intriguingly, under conditions of impaired GC-Tfh-GC-B cell interactions, such as human immunodeficiency virus (HIV) infection, the frequency of these cells is increased. Overall, we predict a role for ILC
FR
in regulating GC-Tfh-GC-B cell interactions and propose they expand in chronic inflammatory conditions.
Margaret O’Connor et al. report a new Innate Lymphoid Cell population in human tonsils and lymph nodes that inhibit the functional interaction of follicular helper T cells and germinal center B cells. They show that this cell population is expanded under chronic HIV infection and results in decreased antibody production, suggesting a potential role for these cells in diseases with dysregulated immune responses.