%0 Journal Article
%T A Non-Coding Oligonucleotide Recruits Cutaneous CD11b+ Cells that Inhibit Thelper Responses and Promote Tregs.
%A Kamal K
%A Richardsdotter-Andersson E
%A Dondalska A
%A Wahren-Herlenius M
%A Spetz AL
%J Adv Sci (Weinh)
%V 0
%N 0
%D 2024 Jun 19
%M 38896803
%F 17.521
%R 10.1002/advs.202400260
%X Skin-resident antigen-presenting cells (APC) play an important role in maintaining peripheral tolerance via immune checkpoint proteins and induction of T regulatory cells (Tregs). However, there is a lack of knowledge on how to expand or recruit immunoregulatory cutaneous cells without causing inflammation. Here, it is shown that administration of a non-coding single-stranded oligonucleotide (ssON) leads to CCR2-dependent accumulation of CD45+CD11b+Ly6C+ cells in the skin that express substantial levels of PD-L1 and ILT3. Transcriptomic analyses of skin biopsies reveal the upregulation of key immunosuppressive genes after ssON administration. Functionally, the cutaneous CD11b+ cells inhibit Th1/2/9 responses and promote the induction of CD4+FoxP3+ T-cells. In addition, ssON treatment of imiquimod-induced inflammation results in significantly reduced Th17 responses. It is also shown that induction of IL-10 production in the presence of cutaneous CD11b+ cells isolated after ssON administrations is partly PD-L1 dependent. Altogether, an immunomodulatory ssON is identified that can be used therapeutically to recruit cutaneous CD11b+ cells with the capacity to dampen Th cells.