@article{Makuyana:2026:10.1126/sciimmunol.adv7969,
author = {Makuyana, N and Seldeslachts, L and Michiels, L and Burton, OT and Hernandez, AR and Ghodsinia, A and Rahman, E and Kops, LM and Singh, K and Naranjo, F and Ali, M and Dashwood, A and Achkir, M and Kouser, L and Lienart, S and Guillaume, S and Naesens, L and Linterman, MA and Wauters, J and Joulia, R and Humblet-Baron, S and Vande, Velde G and Dooley, J and Liston, A},
doi = {10.1126/sciimmunol.adv7969},
journal = {Sci Immunol},
title = {Gene delivery of immunomodulatory cytokines to the lung preserves respiratory function during inflammatory challenge.},
url = {http://dx.doi.org/10.1126/sciimmunol.adv7969},
volume = {11},
year = {2026}
}

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TY  - JOUR
AB  - Respiratory infections that result in severe and life-threatening immune-mediated respiratory decline are a major public health issue. Controlling local respiratory immune reactions without the use of systemic immunosuppressants remains an unmet clinical challenge. We developed a gene delivery system to express anti-inflammatory cytokines in the lung, which reestablishes local immune homeostasis without triggering systemic effects. Using an adeno-associated vector cargo system (AAV6.2-CC10), we induced production of interleukin-2 (IL-2), IL-1 receptor antagonist (IL-1RA), and IL-10 in situ in the lung microenvironment, with no detectable expression or immunological deviation in the peripheral immune system. We demonstrate the effective potential of IL-2, IL-1RA, and IL-10 as immunomodulatory cargos in severe infectious challenge, which reduced respiratory pathology after influenza-associated pulmonary aspergillosis. Thus, the AAV6.2-CC10 platform enables targeted delivery of biologics to the lung, modulates the lung environment, and improves pathology without inducing systemic immune reactions.
AU  - Makuyana,N
AU  - Seldeslachts,L
AU  - Michiels,L
AU  - Burton,OT
AU  - Hernandez,AR
AU  - Ghodsinia,A
AU  - Rahman,E
AU  - Kops,LM
AU  - Singh,K
AU  - Naranjo,F
AU  - Ali,M
AU  - Dashwood,A
AU  - Achkir,M
AU  - Kouser,L
AU  - Lienart,S
AU  - Guillaume,S
AU  - Naesens,L
AU  - Linterman,MA
AU  - Wauters,J
AU  - Joulia,R
AU  - Humblet-Baron,S
AU  - Vande,Velde G
AU  - Dooley,J
AU  - Liston,A
DO  - 10.1126/sciimmunol.adv7969
PY  - 2026///
TI  - Gene delivery of immunomodulatory cytokines to the lung preserves respiratory function during inflammatory challenge.
T2  - Sci Immunol
UR  - http://dx.doi.org/10.1126/sciimmunol.adv7969
UR  - https://www.ncbi.nlm.nih.gov/pubmed/41996474
VL  - 11
ER  - 

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