Clonal Vγ6+Vδ4+ T cells promote IL-17–mediated immunity against Staphylococcus aureus skin infection

Mark C. Marchitto; Carly A. Dillen; Haiyun Liu; Robert J. Miller; Nathan K. Archer; Roger V. Ortines; Martin P. Alphonse; Alina I. Marusina; Alexander A. Merleev; Yu Wang; Bret L. Pinsker; Angel S. Byrd; Isabelle D. Brown; Advaitaa Ravipati; Emily Zhang; Shuting S. Cai; Nathachit Limjunyawong; Xinzhong Dong; Michael R. Yeaman; Scott I. Simon; Wei Shen; Scott K. Durum; Rebecca L. O’Brien; Emanual Maverakis; Lloyd S. Miller

doi:10.1073/pnas.1818256116

Clonal Vγ6⁺Vδ4⁺ T cells promote IL-17–mediated immunity against Staphylococcus aureus skin infection

Mark C. Marchitto, Carly A. Dillen, Haiyun Liu, Robert J. Miller, Nathan K. Archer, Roger V. Ortines, Martin P. Alphonse, Alina I. Marusina, Alexander A. Merleev, Yu Wang, Bret L. Pinsker, Angel S. Byrd, Isabelle D. Brown, Advaitaa Ravipati, Emily Zhang, Shuting S. Cai, Nathachit Limjunyawong, Xinzhong Dong, Michael R. Yeaman, Scott I. SimonWei Shen, Scott K. Durum, Rebecca L. O’Brien, Emanual Maverakis, Lloyd S. Miller

School of Medicine

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

T cell cytokines contribute to immunity against Staphylococcus aureus, but the predominant T cell subsets involved are unclear. In an S. aureus skin infection mouse model, we found that the IL-17 response was mediated by γδ T cells, which trafficked from lymph nodes to the infected skin to induce neutrophil recruitment, proinflammatory cytokines IL-1α, IL-1β, and TNF, and host defense peptides. RNA-seq for TRG and TRD sequences in lymph nodes and skin revealed a single clonotypic expansion of the encoded complementarity-determining region 3 amino acid sequence, which could be generated by canonical nucleotide sequences of TRGV5 or TRGV6 and TRDV4. However, only TRGV6 and TRDV4 but not TRGV5 sequences expanded. Finally, Vγ6⁺ T cells were a predominant γδ T cell subset that produced IL-17A as well as IL-22, TNF, and IFNγ, indicating a broad and substantial role for clonal Vγ6⁺Vδ4⁺ T cells in immunity against S. aureus skin infections.

Original language	English (US)
Pages (from-to)	10917-10926
Number of pages	10
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	166
Issue number	22
DOIs	https://doi.org/10.1073/pnas.1818256116
State	Published - May 28 2019

Keywords

IL-17
Neutrophils
Skin
Staphylococcus aureus
T cells

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.1818256116

Cite this

Marchitto, M. C., Dillen, C. A., Liu, H., Miller, R. J., Archer, N. K., Ortines, R. V., Alphonse, M. P., Marusina, A. I., Merleev, A. A., Wang, Y., Pinsker, B. L., Byrd, A. S., Brown, I. D., Ravipati, A., Zhang, E., Cai, S. S., Limjunyawong, N., Dong, X., Yeaman, M. R., ... Miller, L. S. (2019). Clonal Vγ6⁺Vδ4⁺ T cells promote IL-17–mediated immunity against Staphylococcus aureus skin infection. Proceedings of the National Academy of Sciences of the United States of America, 166(22), 10917-10926. https://doi.org/10.1073/pnas.1818256116

Marchitto, MC, Dillen, CA, Liu, H, Miller, RJ, Archer, NK, Ortines, RV, Alphonse, MP, Marusina, AI, Merleev, AA, Wang, Y, Pinsker, BL, Byrd, AS, Brown, ID, Ravipati, A, Zhang, E, Cai, SS, Limjunyawong, N, Dong, X, Yeaman, MR, Simon, SI, Shen, W, Durum, SK, O’Brien, RL, Maverakis, E & Miller, LS 2019, 'Clonal Vγ6⁺Vδ4⁺ T cells promote IL-17–mediated immunity against Staphylococcus aureus skin infection', Proceedings of the National Academy of Sciences of the United States of America, vol. 166, no. 22, pp. 10917-10926. https://doi.org/10.1073/pnas.1818256116

@article{2117fc7ee051406884d68ff8547dcddd,

title = "Clonal Vγ6+Vδ4+ T cells promote IL-17–mediated immunity against Staphylococcus aureus skin infection",

abstract = "T cell cytokines contribute to immunity against Staphylococcus aureus, but the predominant T cell subsets involved are unclear. In an S. aureus skin infection mouse model, we found that the IL-17 response was mediated by γδ T cells, which trafficked from lymph nodes to the infected skin to induce neutrophil recruitment, proinflammatory cytokines IL-1α, IL-1β, and TNF, and host defense peptides. RNA-seq for TRG and TRD sequences in lymph nodes and skin revealed a single clonotypic expansion of the encoded complementarity-determining region 3 amino acid sequence, which could be generated by canonical nucleotide sequences of TRGV5 or TRGV6 and TRDV4. However, only TRGV6 and TRDV4 but not TRGV5 sequences expanded. Finally, Vγ6+ T cells were a predominant γδ T cell subset that produced IL-17A as well as IL-22, TNF, and IFNγ, indicating a broad and substantial role for clonal Vγ6+Vδ4+ T cells in immunity against S. aureus skin infections.",

keywords = "IL-17, Neutrophils, Skin, Staphylococcus aureus, T cells",

author = "Marchitto, {Mark C.} and Dillen, {Carly A.} and Haiyun Liu and Miller, {Robert J.} and Archer, {Nathan K.} and Ortines, {Roger V.} and Alphonse, {Martin P.} and Marusina, {Alina I.} and Merleev, {Alexander A.} and Yu Wang and Pinsker, {Bret L.} and Byrd, {Angel S.} and Brown, {Isabelle D.} and Advaitaa Ravipati and Emily Zhang and Cai, {Shuting S.} and Nathachit Limjunyawong and Xinzhong Dong and Yeaman, {Michael R.} and Simon, {Scott I.} and Wei Shen and Durum, {Scott K.} and O{\textquoteright}Brien, {Rebecca L.} and Emanual Maverakis and Miller, {Lloyd S.}",

year = "2019",

month = may,

day = "28",

doi = "10.1073/pnas.1818256116",

language = "English (US)",

volume = "166",

pages = "10917--10926",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "22",

}

TY - JOUR

T1 - Clonal Vγ6+Vδ4+ T cells promote IL-17–mediated immunity against Staphylococcus aureus skin infection

AU - Marchitto, Mark C.

AU - Dillen, Carly A.

AU - Liu, Haiyun

AU - Miller, Robert J.

AU - Archer, Nathan K.

AU - Ortines, Roger V.

AU - Alphonse, Martin P.

AU - Marusina, Alina I.

AU - Merleev, Alexander A.

AU - Wang, Yu

AU - Pinsker, Bret L.

AU - Byrd, Angel S.

AU - Brown, Isabelle D.

AU - Ravipati, Advaitaa

AU - Zhang, Emily

AU - Cai, Shuting S.

AU - Limjunyawong, Nathachit

AU - Dong, Xinzhong

AU - Yeaman, Michael R.

AU - Simon, Scott I.

AU - Shen, Wei

AU - Durum, Scott K.

AU - O’Brien, Rebecca L.

AU - Maverakis, Emanual

AU - Miller, Lloyd S.

PY - 2019/5/28

Y1 - 2019/5/28

N2 - T cell cytokines contribute to immunity against Staphylococcus aureus, but the predominant T cell subsets involved are unclear. In an S. aureus skin infection mouse model, we found that the IL-17 response was mediated by γδ T cells, which trafficked from lymph nodes to the infected skin to induce neutrophil recruitment, proinflammatory cytokines IL-1α, IL-1β, and TNF, and host defense peptides. RNA-seq for TRG and TRD sequences in lymph nodes and skin revealed a single clonotypic expansion of the encoded complementarity-determining region 3 amino acid sequence, which could be generated by canonical nucleotide sequences of TRGV5 or TRGV6 and TRDV4. However, only TRGV6 and TRDV4 but not TRGV5 sequences expanded. Finally, Vγ6+ T cells were a predominant γδ T cell subset that produced IL-17A as well as IL-22, TNF, and IFNγ, indicating a broad and substantial role for clonal Vγ6+Vδ4+ T cells in immunity against S. aureus skin infections.

AB - T cell cytokines contribute to immunity against Staphylococcus aureus, but the predominant T cell subsets involved are unclear. In an S. aureus skin infection mouse model, we found that the IL-17 response was mediated by γδ T cells, which trafficked from lymph nodes to the infected skin to induce neutrophil recruitment, proinflammatory cytokines IL-1α, IL-1β, and TNF, and host defense peptides. RNA-seq for TRG and TRD sequences in lymph nodes and skin revealed a single clonotypic expansion of the encoded complementarity-determining region 3 amino acid sequence, which could be generated by canonical nucleotide sequences of TRGV5 or TRGV6 and TRDV4. However, only TRGV6 and TRDV4 but not TRGV5 sequences expanded. Finally, Vγ6+ T cells were a predominant γδ T cell subset that produced IL-17A as well as IL-22, TNF, and IFNγ, indicating a broad and substantial role for clonal Vγ6+Vδ4+ T cells in immunity against S. aureus skin infections.

KW - IL-17

KW - Neutrophils

KW - Skin

KW - Staphylococcus aureus

KW - T cells

UR - http://www.scopus.com/inward/record.url?scp=85066232618&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85066232618&partnerID=8YFLogxK

U2 - 10.1073/pnas.1818256116

DO - 10.1073/pnas.1818256116

M3 - Article

C2 - 31088972

AN - SCOPUS:85066232618

SN - 0027-8424

VL - 166

SP - 10917

EP - 10926

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 22

ER -