Dermal γδ T Cells Do Not Freely Re-Circulate Out of Skin and Produce IL-17 to Promote Neutrophil Infiltration during Primary Contact Hypersensitivity

• Published in: PloS one Vol. 12; no. 1; p. e0169397
• Main Authors: Jiang, Xiaodong, Park, Chang Ook, Geddes Sweeney, Jenna, Yoo, Min Jae, Gaide, Olivier, Kupper, Thomas Seth
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.01.2017; Public Library of Science (PLoS)
• Subjects: Animals; Biology and Life Sciences; CD103 antigen; CD11b antigen; CD69 antigen; Cell migration; Computer memory; Contact dermatitis; Cytokines; Dermatitis; Dermatitis, Contact - genetics; Dermatitis, Contact - immunology; Dermatitis, Contact - pathology; Dermatology; Dermis - immunology; Dermis - pathology; Dinitrofluorobenzene; Ear; Effector cells; Epidermis; Homing; Homing receptors; Hypersensitivity; Immunological memory; Infiltration; Inflammation; Interleukin 17; Interleukin 22; Interleukin-17 - genetics; Interleukin-17 - immunology; Interleukins - genetics; Interleukins - immunology; Leukocytes (neutrophilic); Lymphocytes; Lymphocytes T; Medical schools; Medicine and Health Sciences; Memory cells; Mice; Mice, Knockout; Neutralization; Neutrophil Infiltration; Neutrophils; Neutrophils - immunology; Neutrophils - pathology; Population; Receptors; Receptors, Antigen, T-Cell, gamma-delta - genetics; Receptors, Antigen, T-Cell, gamma-delta - immunology; Research and Analysis Methods; Rodents; Skin; Skin diseases; Swelling; T cell receptors; T-cell receptor; T-Lymphocytes - immunology; T-Lymphocytes - pathology
• DOI: 10.1371/journal.pone.0169397
• ISSN: 1932-6203

The role of mouse dermal γδ T cells in inflammatory skin disorders and host defense has been studied extensively. It is known that dendritic epidermal T cells (DETC) have a monomorphic γδ T cell receptor (TCR) and reside in murine epidermis from birth. We asked if dermal γδ cells freely re-circulated out of skin, or behaved more like dermal resident memory T cells (TRM) in mice. We found that, unlike epidermal γδ T cells (DETC), dermal γδ cells are not homogeneous with regard to TCR, express the tissue resident T cell markers CD69 and CD103, bear skin homing receptors, and produce IL-17 and IL-22. We created GFP+: GFP- parabiotic mice and found that dermal γδ T cells re-circulate very slowly-more rapidly than authentic αβ TCR TRM, but more slowly than the recently described dermal αβ TCR T migratory memory cells (TMM). Mice lacking the TCR δ gene (δ-/-) had a significant reduction of 2,4-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity (CHS). We created mice deficient in dermal γδ T cells but not DETC, and these mice also showed a markedly reduced CHS response after DNFB challenge. The infiltration of effector T cells during CHS was not reduced in dermal γδ T cell-deficient mice; however, infiltration of Gr-1+CD11b+ neutrophils, as well as ear swelling, was reduced significantly. We next depleted Gr-1+ neutrophils in vivo, and demonstrated that neutrophils are required for ear swelling, the accepted metric for a CHS response. Depletion of IL-17-producing dermal Vγ4+ cells and neutralization of IL-17 in vivo, respectively, also led to a significantly reduced CHS response and diminished neutrophil infiltration. Our findings here suggest that dermal γδ T cells have an intermediate phenotype of T cell residence, and play an important role in primary CHS through producing IL-17 to promote neutrophil infiltration.