TY - JOUR T1 - CD6 is expressed on human airway and blood innate lymphoid cells (ILCs) and is upregulated by epithelial alarmins IL-33 and TSLP JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2020.613 VL - 56 IS - suppl 64 SP - 613 AU - Jana Badrani AU - Kellen Cavagnero AU - Cherie Ng AU - Jeanette Ampudia AU - Stephen Connelly AU - Pragnya Desai AU - Cindy Koziol-White AU - Reynold Panettieri AU - Davide Broide AU - Richard Kurten AU - Taylor Doherty Y1 - 2020/09/07 UR - http://erj.ersjournals.com/content/56/suppl_64/613.abstract N2 - Rationale: Innate lymphoid cells (ILCs) are recently discovered counterparts of T helper subsets. ILC2s produce type 2 cytokines in response to epithelial alarmins IL-33 and TSLP, contribute to asthma features in animal models, and are elevated in human asthma. CD6 is a co-stimulatory receptor that contributes to pathogenic T cell responses in allergic and autoimmune inflammation. The role of CD6 on ILC subsets is unknown.Methods: Flow cytometry for CD6 expression on ILC subsets was performed on human blood, lung, and nasal polyps. ILC subsets (CD45+lineage- lymphocytes) were identified as follows: ILC1s as CD127+CD117-CRTH2-; ILC2s as CD127+CRTH2+; and ILC3s as CD127+CD117+CRTH2-. RNA-seq was performed with sorted CD6+ and CD6- blood ILC subsets. Human blood cells were cultured with IL-33, TSLP, or both and ILC2 CD6 expression levels assessed. Mice were challenged with IL-33, and levels of lung ILC2 CD6 were determined.Results: CD6 was expressed on subpopulations of all human airway ILC subsets (nasal polyps and lung), including lung tissue from a donor with fatal asthma. Bimodal CD6 expression was detected on human blood ILCs, and RNA-Seq revealed unique transcriptomes of CD6+ and CD6-ILCs. Blood ILC2s stimulated with IL33 and/or TSLP revealed increased CD6 expression compared with unstimulated controls. Mouse lung ILC2 CD6 expression was induced by IL-33.Conclusions: CD6 is expressed on human airway ILCs and is induced on ILC2s by epithelial cytokines critical to asthma. Given the role of CD6 in driving pathogenic T cell responses, strategies targeting CD6 may be relevant to modulating both ILC- and T cell-driven responses in asthma.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 613.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -