title: A Human Lin-CD123+CD127lowPopulation Endowed with ILC Features and Migratory Capabilities Contributes to Immunopathological Hallmarks of Psoriasis.
abstract: Innate lymphoid cells (ILC) are members of a heterogeneous family with a lymphoid origin that mimics the T helper (Th) cytokine profile. ILC are involved in early effector cytokine-mediated responses during infections in peripheral tissues. ILC also play an important role in chronic skin inflammatory diseases, including psoriasis. Although classical ILC express CD127, it has been recently reported that the presence of non-classical CD127-ILC populations and an early ILC precursor (EILP) CD127low. ILC development has predominately been investigated in mouse models. However, in humans, different transcription factors have been described for ILC identification. NFIL3 (nuclear factor, IL-3 regulated) is crucial for ILC development in response to IL-7. CD123 (IL-3Rα) is usually used to exclude basophils during ILC identification, however, it is unknown if in response to IL-3, NFIL3 could be relevant to induce ILC features in Lin-CD123+populations in addition, is also unknown whether peripheral blood (PB) population with ILC features may have skin-homing potential to participate in skin inflammatory chronic diseases. Here, we report a Lin-CD123+CD127lowCD7+CLA+population that share some phenotypic properties with basophils, but expresses several transcription factors for ILC commitment such as inhibitor of DNA binding 2 (Id2), NFIL3, promyelocytic leukemia zinc finger (PLZF), thymocyte selection-associated high-mobility group box protein (TOX), and T cell factor-1 (TCF-1). In addition, this population expresses different ILC markers: CD132, CD90, CD161, α4 integrin, c-Kit, CRTH2, AhR, and IL-23R. IL-3 prevents apoptosis and increases their NFIL3, TOX, and PLZF expression. In PB, the CD123+CD127lowpopulation is predominantly a conspicuous population that expresses T-bet and RORγt. The Lin-CD123+CD127lowpopulation in PB has a limited Th type cytokine expression and highly expresses IL-8. The Lin-CD123+CD127lowpopulation expresses skin-homing receptors (cutaneous lymphocyte antigen and CXCR4) and transmigrates through endothelial cells in response to SDF-1. An equivalent Lin-CD123lowpopulation was identified in control skin, which shows a broader phenotypic diversity and cytokine production, including IL-22 and IL-17. Remarkably, the CD123lowpopulation in the lesion and non-lesion skin of psoriasis patients expresses IL-17 and IL-22. Our findings suggest the identification of an alternative Lin-CD123+CD127lowpopulation with ILC features endowed with migratory capabilities that might contribute to immunopathological hallmarks of psoriasis.
authors.affiliation: Unidad de Investigación Médica en Inmunoquímica Hospital de Especialidades Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico; Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico.
authors.forename: Luz María
authors.initials: LM
authors.lastname: Mora-Velandia
authors.affiliation: Unidad de Investigación Médica en Inmunoquímica Hospital de Especialidades Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico; Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico.
authors.forename: Octavio
authors.initials: O
authors.lastname: Castro-Escamilla
authors.affiliation: Unidad de Investigación Médica en Inmunoquímica Hospital de Especialidades Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social , Mexico City , Mexico.
authors.forename: Andrés González
authors.initials: AG
authors.lastname: Méndez
authors.affiliation: Unidad de Investigación Médica en Inmunoquímica Hospital de Especialidades Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social , Mexico City , Mexico.
authors.forename: Cristina
authors.initials: C
authors.lastname: Aguilar-Flores
authors.affiliation: Unidad de Investigación en Enfermedades Oncológicas, Hospital de Oncología, Centro Médico Nacional 'Siglo XXI' , Mexico City , Mexico.
authors.forename: Martha
authors.initials: M
authors.lastname: Velázquez-Avila
authors.affiliation: División de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico; Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México "Federico Gómez", Mexico City, Mexico.
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Tussié-Luna
authors.affiliation: Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública , Cuernavaca, Morelos , Mexico.
authors.forename: Juan
authors.initials: J
authors.lastname: Téllez-Sosa
authors.affiliation: Centro Dermatológico "Dr. Ladislao de la Pascua", Secretaria de Salud de la Ciudad de México , Mexico City , Mexico.
authors.forename: César
authors.initials: C
authors.lastname: Maldonado-García
authors.affiliation: Centro Dermatológico "Dr. Ladislao de la Pascua", Secretaria de Salud de la Ciudad de México , Mexico City , Mexico.
authors.forename: Fermín
authors.initials: F
authors.lastname: Jurado-Santacruz
authors.affiliation: Unidad de Investigación Médica en Inmunoquímica Hospital de Especialidades Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social , Mexico City , Mexico.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ferat-Osorio
authors.affiliation: Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública , Cuernavaca, Morelos , Mexico.
authors.forename: Jesus
authors.initials: J
authors.lastname: Martínez-Barnetche
authors.affiliation: Unidad de Investigación en Enfermedades Oncológicas, Hospital de Oncología, Centro Médico Nacional 'Siglo XXI' , Mexico City , Mexico.
authors.forename: Rosana
authors.initials: R
authors.lastname: Pelayo
authors.affiliation: Unidad de Investigación Médica en Inmunoquímica Hospital de Especialidades Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social , Mexico City , Mexico.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Bonifaz
keywords: CXCR4 axis; IL-17; IL-3Rα; SDF-1; innate lymphoid cells; psoriasis; skin inflammation