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Adenosine deaminase-1 (ADA-1) induces maturation and skewing of cytokine and chemokine production in dendritic cells to improve adaptive immune responses
Journal article   Peer reviewed

Adenosine deaminase-1 (ADA-1) induces maturation and skewing of cytokine and chemokine production in dendritic cells to improve adaptive immune responses

Gina Cusimano, Marita Chakhtoura, Bhavani Taramangalam, Jennifer Connors, Michele A. Kutzler and Elias Haddad
The Journal of immunology (1950), v 208(1_Supplement), pp 164-164.20
01 May 2022
DOI: https://doi.org/10.4049/jimmunol.208.Supp.164.20

Abstract

Abstract Dendritic cells (DCs) are critical mediators of antigen-specific immunity through their ability to present antigen and drive T cell differentiation into different effector subsets such as follicular helper T cells (TFH). TFH cells provide both physical and cytokine-mediated stimuli to B cells resulting in somatic hypermutation and class-switching of B cell receptors. Molecules that target TFH cells, such as adenosine deaminase-1 (ADA-1), would improve humoral immunity. We have previously demonstrated that co-delivery of plasmid-encoded adenosine deaminase with an HIV-1 envelope and SARS-CoV-2 DNA vaccines in vivo, enhanced both humoral and cellular responses. However, the mechanism by which ADA-1 is acting as an adjuvant remains to be elucidated. To this end, we treated monocyte-derived DCs from healthy human donors in vitro with recombinant ADA-1 protein and evaluated the expression of maturation markers, cytokines and chemokines. ADA-1-treated DCs had a significantly increased expression of CD40 and CD86 as well as HLA-DR compared to their unstimulated, immature counterparts. The level of co-stimulatory marker and HLA-DR expression on ADA-1-treated DCs was similar to that on LPS/IFN-γ-treated DCs, indicating ADA-1-mediated DC maturation. ADA-1-treated DCs also exhibited a significant increase in IL-6, IL-1β and CXCL13 expression. IL-6 is a key pro-TFH cytokine and IL-1β and CXCL13 may play a role in TFH cell differentiation, function, and proliferation. Ongoing studies are aimed to drive ADA-1 overexpression in DCs and evaluate effects on antigen presentation. Overall, elucidating the mechanism of ADA-1’s adjuvanticity will allow for its progression as a clinical adjuvant. This work was supported by funding to Dr. Elias Haddad from NIH 5RO1AI106482-01A and 1U19 AI128910-01.

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Immunology
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