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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0901059v1 183/3/2142    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Doisne, J.-M. Articles by Benlagha, K. PubMed PubMed Citation Articles by Doisne, J.-M. Articles by Benlagha, K.

Skin and Peripheral Lymph Node Invariant NKT Cells Are Mainly Retinoic Acid Receptor-Related Orphan Receptor t⁺ and Respond Preferentially under Inflammatory Conditions¹

Jean-Marc Doisne^*, Chantal Becourt^*, Latiffa Amniai^*, Nadia Duarte^*, Jean-Benoît Le Luduec, Gérard Eberl and Kamel Benlagha^2,*

^* INSERM Unité 561/Groupe AVENIR, Hôpital Cochin St. Vincent de Paul, Université Descartes, Paris, France; INSERM Unité 851, Institut Fédératif de Recherche 128, Lyon, France; and Institut Pasteur, Laboratory of Lymphoid Tissue Development, Centre National de la Recherche Scientifique Unité de Recherche Associée 1961, Paris, France

Lymph nodes (LNs) have been long considered as comprising few invariant NKT (iNKT) cells, and these cells have not been studied extensively. In this study, we unravel the existence of stable rather than transitional LN-resident NK1.1^– iNKT cell populations. We found the one resident in peripheral LNs (PLNs) to comprise a major IL-17-producing population and to express the retinoic acid receptor-related orphan receptor t (RORt). These cells respond to their ligand -galactosylceramide (-GalCer) in vivo by expanding dramatically in the presence of LPS, providing insight into how this rare population could have an impact in immune responses to infection. PLN-resident RORt⁺ NK1.1^– iNKT cells express concomitantly CCR6, the integrin -chain _E (CD103), and IL-1R type I (CD121a), indicating that they might play a role in inflamed epithelia. Accordingly, skin epithelia comprise a major RORt⁺ CCR6⁺CD103⁺CD121a⁺ NK1.1^– cell population, reflecting iNKT cell composition in PLNs. Importantly, both skin and draining PLN RORt⁺ iNKT cells respond preferentially to inflammatory signals and independently of IL-6, indicating that they could play a nonredundant role during inflammation. Overall, our study indicates that RORt⁺ iNKT cells could play a major role in the skin during immune responses to infection and autoimmunity.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by INSERM "Groupe AVENIR" Grant R04193KS, Fondation pour la Recherche Médicale Grant INE20051105133, and Agence Nationale pour la Recherche Grant R07119KS, awarded to K.B.

² Address correspondence and reprint requests to Dr. Kamel Benlagha, INSERM Unité 561, 82 Avenue Denfert Rochereau, 75014 Paris, France. E-mail address: kamel.benlagha{at}inserm.fr

³ Abbreviations used in this paper: iNKT, invariant NKT; 7-AAD, 7-aminoactinomycin D; -GalCer, -galactosylceramide; BM-DC, bone marrow-derived dendritic cell; DC, dendritic cell; DN, double negative; LN, lymph node; PLN, peripheral LN; RORt, retinoic acid receptor-related orphan receptor t; TPA, 12-O-tetradecanoylphorbol-13-acetate; WT, wild type.

⁴ The online version of this article contains supplemental material.