Keratinocyte-intrinsic MHCII Expression Controls Microbiota-induced Th1 Cell Responses

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2019 Nov 2

PMID 31672911

Citations 34

Authors

Samira Tamoutounour

Seong-Ji Han

Julie Deckers

Michael G Constantinides

Charlotte Hurabielle

Oliver J Harrison

Nicolas Bouladoux

Jonathan L Linehan

Verena M Link

Ivan Vujkovic-Cvijin

Paula Juliana Perez-Chaparro

Stephan P Rosshart

Barbara Rehermann

Vanja Lazarevic

Yasmine Belkaid

Affiliations

Soon will be listed here.

Abstract

The cross-talk between the microbiota and the immune system plays a fundamental role in the control of host physiology. However, the tissue-specific factors controlling this dialogue remain poorly understood. Here we demonstrate that T cell responses to commensal colonization are associated with the development of organized cellular clusters within the skin epithelium. These organized lymphocyte clusters are surrounded by keratinocytes expressing a discrete program associated with antigen presentation and antimicrobial defense. Notably, IL-22-mediated keratinocyte-intrinsic MHC class II expression was required for the selective accumulation of commensal-induced IFN-γ, but not IL-17A-producing CD4 T cells within the skin. Taking these data together, this work uncovers an unexpected role for MHC class II expression by keratinocytes in the control of homeostatic type 1 responses to the microbiota. Our findings have important implications for the understanding of the tissue-specific rules governing the dialogue between a host and its microbiota.

Citing Articles

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References

Sabat R, Ouyang W, Wolk K . Therapeutic opportunities of the IL-22-IL-22R1 system. Nat Rev Drug Discov. 2014; 13(1):21-38. DOI: 10.1038/nrd4176. View

Serbina N, Pamer E . Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol. 2006; 7(3):311-7. DOI: 10.1038/ni1309. View

Gaboriau-Routhiau V, Rakotobe S, Lecuyer E, Mulder I, Lan A, Bridonneau C . The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity. 2009; 31(4):677-89. DOI: 10.1016/j.immuni.2009.08.020. View

Klein Wolterink R, Kleinjan A, van Nimwegen M, Bergen I, de Bruijn M, Levani Y . Pulmonary innate lymphoid cells are major producers of IL-5 and IL-13 in murine models of allergic asthma. Eur J Immunol. 2012; 42(5):1106-16. DOI: 10.1002/eji.201142018. View

Harrison O, Linehan J, Shih H, Bouladoux N, Han S, Smelkinson M . Commensal-specific T cell plasticity promotes rapid tissue adaptation to injury. Science. 2018; 363(6422). PMC: 7304459. DOI: 10.1126/science.aat6280. View

Dietrich C . Antioxidant Functions of the Aryl Hydrocarbon Receptor. Stem Cells Int. 2016; 2016:7943495. PMC: 5088273. DOI: 10.1155/2016/7943495. View

Pickert G, Neufert C, Leppkes M, Zheng Y, Wittkopf N, Warntjen M . STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing. J Exp Med. 2009; 206(7):1465-72. PMC: 2715097. DOI: 10.1084/jem.20082683. View

Naik S, Bouladoux N, Wilhelm C, Molloy M, Salcedo R, Kastenmuller W . Compartmentalized control of skin immunity by resident commensals. Science. 2012; 337(6098):1115-9. PMC: 3513834. DOI: 10.1126/science.1225152. View

Vivier E, Artis D, Colonna M, Diefenbach A, Di Santo J, Eberl G . Innate Lymphoid Cells: 10 Years On. Cell. 2018; 174(5):1054-1066. DOI: 10.1016/j.cell.2018.07.017. View

10.

Nagao K, Kobayashi T, Moro K, Ohyama M, Adachi T, Kitashima D . Stress-induced production of chemokines by hair follicles regulates the trafficking of dendritic cells in skin. Nat Immunol. 2012; 13(8):744-52. PMC: 4115277. DOI: 10.1038/ni.2353. View

11.

Morillon 2nd Y, Manzoor F, Wang B, Tisch R . Isolation and transplantation of different aged murine thymic grafts. J Vis Exp. 2015; (99):e52709. PMC: 4542632. DOI: 10.3791/52709. View

12.

Biton M, Haber A, Rogel N, Burgin G, Beyaz S, Schnell A . T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation. Cell. 2018; 175(5):1307-1320.e22. PMC: 6239889. DOI: 10.1016/j.cell.2018.10.008. View

13.

Black A, Ardern-Jones M, Kasprowicz V, Bowness P, Jones L, Bailey A . Human keratinocyte induction of rapid effector function in antigen-specific memory CD4+ and CD8+ T cells. Eur J Immunol. 2007; 37(6):1485-93. DOI: 10.1002/eji.200636915. View

14.

Love M, Huber W, Anders S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15(12):550. PMC: 4302049. DOI: 10.1186/s13059-014-0550-8. View

15.

Carr M, McVittie E, Guy K, Gawkrodger D, Hunter J . MHC class II antigen expression in normal human epidermis. Immunology. 1986; 59(2):223-7. PMC: 1453164. View

16.

Mao K, Baptista A, Tamoutounour S, Zhuang L, Bouladoux N, Martins A . Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism. Nature. 2018; 554(7691):255-259. DOI: 10.1038/nature25437. View

17.

Natsuaki Y, Egawa G, Nakamizo S, Ono S, Hanakawa S, Okada T . Perivascular leukocyte clusters are essential for efficient activation of effector T cells in the skin. Nat Immunol. 2014; 15(11):1064-9. DOI: 10.1038/ni.2992. View

18.

Linehan J, Harrison O, Han S, Byrd A, Vujkovic-Cvijin I, Villarino A . Non-classical Immunity Controls Microbiota Impact on Skin Immunity and Tissue Repair. Cell. 2018; 172(4):784-796.e18. PMC: 6034182. DOI: 10.1016/j.cell.2017.12.033. View

19.

Mueller S, Mackay L . Tissue-resident memory T cells: local specialists in immune defence. Nat Rev Immunol. 2015; 16(2):79-89. DOI: 10.1038/nri.2015.3. View

20.

Schauber J, Gallo R . Expanding the roles of antimicrobial peptides in skin: alarming and arming keratinocytes. J Invest Dermatol. 2007; 127(3):510-2. DOI: 10.1038/sj.jid.5700761. View