Skin and peripheral lymph node invariant NKT cells are mainly retinoic acid receptor-related orphan receptor (gamma)t+ and respond preferentially under inflammatory conditions.
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 (gamma)t (ROR(gamma)t). These cells respond to their ligand alpha-galactosylceramide (alpha-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 ROR(gamma)t(+) NK1.1(-) iNKT cells express concomitantly CCR6, the integrin alpha-chain alpha(E) (CD103), and IL-1R type I (CD121a), indicating that they might play a role in inflamed epithelia. Accordingly, skin epithelia comprise a major ROR(gamma)t(+) CCR6(+)CD103(+)CD121a(+) NK1.1(-) cell population, reflecting iNKT cell composition in PLNs. Importantly, both skin and draining PLN ROR(gamma)t(+) 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 ROR(gamma)t(+) iNKT cells could play a major role in the skin during immune responses to infection and autoimmunity.
Doisne
Jean-Marc
JM
INSERM Unité 561/Groupe AVENIR, Hôpital Cochin St Vincent de Paul, Université Descartes, Paris, France.
Becourt
Chantal
C
Amniai
Latiffa
L
Duarte
Nadia
N
Le Luduec
Jean-Benoît
JB
Eberl
Gérard
G
Benlagha
Kamel
K
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000473:pathology; D005699:Galactosylceramides / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D020381:Interleukin-17; D015850:Interleukin-6 / Q000172:deficiency; D008198:Lymph Nodes / Q000166:cytology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000276:immunology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D012867:Skin / Q000166:cytology* / Q000473:pathology
D005699:Galactosylceramides; D020381:Interleukin-17; D015850:Interleukin-6; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C539901:Rorc protein, mouse; C493154:alpha-galactosylceramide