Background: On the basis of the mounting evidence that type 17 T (T17) cells and increased IL-17 play a key role in driving hidradenitis suppurativa (HS) lesion development, biologic agents used previously in psoriasis that block signaling of IL-17A and/or IL-17F isoforms have been repurposed to treat HS.
Objective: Our research aimed to characterize the transcriptome of HS T17 cells compared to the transcriptome of psoriasis T17 cells, along with their ligand-receptor interactions with neighborhood immune cell subsets.
Methods: Single-cell data of 12,300 cutaneous immune cells from 8 deroofing surgical HS skin samples including dermal tunnels were compared to single-cell data of psoriasis skin (19,525 cells from 11 samples) and control skin (11,920 cells from 10 samples). All single-cell data were generated by the same protocol.
Results: HS T17 cells expressed lower levels of IL23R and higher levels of IL1R1 and IL17F compared to psoriasis T17 cells (P < .05). HS Treg cells expressed higher levels of IL1R1 and IL17F compared to psoriasis Treg cells (P < .05). Semimature dendritic cells were the major immune cell subsets expressing IL1B in HS, and IL-1β ligand-receptor interactions between semimature dendritic cells and T17 cells were increased in HS compared to psoriasis (P < .05). HS dermal tunnel keratinocytes expressed inflammatory cytokines (IL17C, IL1A, IL1B, and IL6) that differed from the HS epidermis keratinocytes (IL36G) (P < .05). IL6, which synergizes with IL1B to maintain cytokine expression in T17 cells, was mainly expressed by fibroblasts in HS, which also expressed IL11 inflammatory fibroblast genes (IL11, IL24, IL6, and POSTN) involved in the paracrine IL-1/IL-6 loop.
Conclusion: The IL-1β-T17 cell cytokine axis is likely a dominant pathway in HS with HS T17 cells activated by IL-1β signaling, unlike psoriasis T17 cells, which are activated by IL-23 signaling.
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http://dx.doi.org/10.1016/j.jaci.2023.05.012 | DOI Listing |
Int J Mol Sci
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Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Universidad Autónoma de Madrid (UAM), 28040 Madrid, Spain.
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Department of Microbiology & Immunology, University of South Alabama, Mobile, Alabama, United States.
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October 2024
Department of Neurosciences & Psychiatry, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
Schizophrenia is a neuropsychiatric illness characterized by altered neurotransmission, in which adenosine, a modulator of glutamate and dopamine, plays a critical role that is relatively unexplored in the human brain. In the present study, postmortem human brain tissue from the anterior cingulate cortex (ACC) of individuals with schizophrenia ( = 20) and sex- and age-matched control subjects without psychiatric illness ( = 20) was obtained from the Bronx-Mount Sinai NIH Brain and Tissue Repository. Enriched populations of ACC pyramidal neurons were isolated using laser microdissection (LMD).
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School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, P.R. China.
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Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, 720 Westview Dr. SW, Atlanta, GA 30310, USA.
MoMo30 is an antiviral protein isolated from aqueous extracts of L. (Senegalese bitter melon). Previously, we demonstrated MoMo30's antiviral activity against HIV-1.
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