IL-21-IgFc immunotherapy alters transcriptional landscape of lymph node cells leading to enhanced flu vaccine response in aging and SIV infection.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_8B909D7DFBF2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
IL-21-IgFc immunotherapy alters transcriptional landscape of lymph node cells leading to enhanced flu vaccine response in aging and SIV infection.
Journal
Aging cell
Author(s)
Pallikkuth S., Kvistad D., Sirupangi T., Kizhner A., Pahwa R., Cameron M.J., Richardson B., Williams S., Ayupe A., Brooks M., Petrovas C., Villinger F., Pahwa S.
ISSN
1474-9726 (Electronic)
ISSN-L
1474-9718
Publication state
Published
Issued date
11/2023
Peer-reviewed
Oui
Volume
22
Number
11
Pages
e13984
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Aging people living with HIV (PWH) frequently manifest impaired antibody (Ab) responses to seasonal flu vaccination which has been attributed to ongoing inflammation and immune activation. We have recently reported a similar scenario in old simian immunodeficiency virus (SIV) infected rhesus macaques (RM) with controlled viremia and have been able to compensate for this deficiency by immunotherapy with interleukin (IL)-21-IgFc. To understand the underlying mechanisms of IL-21-induced immunomodulation leading to enhanced flu vaccine response in aging and SIV, we have investigated draining lymph node (LN) cells of IL-21-treated and -untreated animals at postvaccination. We observed IL-21-induced proliferation of flu-specific LN memory CD4 T cells, expansion of B cells expressing IL-21 receptor (IL-21R), and modest expansion of T follicular helper cells (Tfh) co-expressing T-cell immunoreceptor with Ig and ITIM domains (TIGIT) and DNAX accessory molecule (DNAM-1). Transcriptional analysis of LN cells of IL-21-treated animals revealed significant inhibition of germinal center (GC) Tfh and B-cell interferon signaling pathways along with enhanced B-cell development and antigen presentation pathways. We conclude that IL-21 treatment at the time of flu vaccination in aging SIV-infected animals modulates the inductive LN GC activity, to reverse SIV-associated LN Tfh and B-cell dysfunction. IL-21 is a potential candidate molecule for immunotherapy to enhance flu vaccine responses in aging PWH who have deficient antibody responses.
Keywords
Humans, Animals, Influenza Vaccines, Simian Acquired Immunodeficiency Syndrome, T-Lymphocytes, Helper-Inducer, Macaca mulatta, Lymph Nodes, Interleukins/genetics, Simian Immunodeficiency Virus/physiology, Vaccination, IL-21 and Tfh cells, IL-21 and vaccine response, aging and SIV, aging and immune response, immunomodulation in aging
Pubmed
Web of science
Open Access
Yes
Create date
19/09/2023 8:36
Last modification date
23/12/2023 8:14
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