TY - JOUR
T1 - IgM Plasma Cells Reside in Healthy Skin and Accumulate with Chronic Inflammation
AU - Wilson, R. Paul
AU - McGettigan, Shannon E.
AU - Dang, Van Duc
AU - Kumar, Anil
AU - Cancro, Michael P.
AU - Nikbakht, Neda
AU - Stohl, William
AU - Debes, Gudrun F.
N1 - Funding Information:
We thank John Riley and Carolina Lopez for protocols for RNA isolation; Stephen Nutt (Walter and Eliza Hall Institute of Medical Research, Australia) for Blimp-1GFP mice; the Penn Skin Biology and Diseases Resource-based Center for human skin samples; Amanda Schmidt for establishing ELISPOT assays; Mufei Liu, Samantha Measner, Jack Ringe, and Michael Lee for excellent technical assistance; and Jean Scholz for sharing antibodies. We thank Justin Jesse (Leica Biosystems) for establishing human immunohistochemistry staining. We are indebted to Aimee Payne, Dave Allman, Malissa Diehl, and Skye Geherin for helpful discussion and advice along the way. We thank Zia Rahman for critical comments on the manuscript. This work was supported in parts by NIH grants R01AR067751 and R01AI127389 to GFD, and an Ethel Brown Foerderer Foundation Fellowship from Thomas Jefferson University and T32AI134646 to SEM. Conceptualization: RPW, GFD; Formal Analysis: RPW, SEM, VDD, AK, GFD; Funding Acquisition: SEM, GFD; Investigation: RPW, SEM, VDD, AK, WS, GFD; Methodology: RPW, SEM, MPC, NN, WS, GFD; Resources: MPC, NN, WS, GFD; Supervision: GFD, WS; Validation: RPW, SEM, VDD, AK, GFD; Visualization: RPW, SEM, VDD, GFD; Writing - Original Draft Preparation: RPW, VDD, GFD; Writing - Review and Editing: RPW, SEM, VDD, AK, MPC, NN, WS, GFD
Funding Information:
This work was supported in parts by NIH grants R01AR067751 and R01AI127389 to GFD, and an Ethel Brown Foerderer Foundation Fellowship from Thomas Jefferson University and T32AI134646 to SEM.
Publisher Copyright:
© 2019 The Authors
PY - 2019/12
Y1 - 2019/12
N2 - Antibodies are key to cutaneous host defense and inflammation. Despite their importance, the mechanisms by which skin antibodies are sustained are poorly described. Here, we identified that, in addition to antibody production in lymphoid tissues, plasma cells reside in healthy mouse and human skin. In naïve mice, IgM was the predominant isotype produced in skin. Skin plasma cells developed independently of T cells and microbiota. Importantly, chronic skin inflammation promoted the massive accumulation of IgM-secreting cells, and cutaneous immunization directed both T cell–dependent and –independent antigen-specific IgM-secreting cells into skin. Unlike their counterparts in lymphoid tissues, cutaneous IgM-secreting cells were completely dependent on survival factors such as a proliferation-inducing ligand or B cell–activating factor, which were constitutively expressed and upregulated during inflammation in skin. Our data support a model in which skin plasma cells supply natural and adaptive IgM to the cutaneous environment, thereby supporting homeostatic skin barrier functions and providing defense against pathogen intrusion. Our results are also of potential relevance for manipulation of cutaneous plasma cells in inflammatory skin diseases or cutaneous plasma cell malignancies.
AB - Antibodies are key to cutaneous host defense and inflammation. Despite their importance, the mechanisms by which skin antibodies are sustained are poorly described. Here, we identified that, in addition to antibody production in lymphoid tissues, plasma cells reside in healthy mouse and human skin. In naïve mice, IgM was the predominant isotype produced in skin. Skin plasma cells developed independently of T cells and microbiota. Importantly, chronic skin inflammation promoted the massive accumulation of IgM-secreting cells, and cutaneous immunization directed both T cell–dependent and –independent antigen-specific IgM-secreting cells into skin. Unlike their counterparts in lymphoid tissues, cutaneous IgM-secreting cells were completely dependent on survival factors such as a proliferation-inducing ligand or B cell–activating factor, which were constitutively expressed and upregulated during inflammation in skin. Our data support a model in which skin plasma cells supply natural and adaptive IgM to the cutaneous environment, thereby supporting homeostatic skin barrier functions and providing defense against pathogen intrusion. Our results are also of potential relevance for manipulation of cutaneous plasma cells in inflammatory skin diseases or cutaneous plasma cell malignancies.
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U2 - 10.1016/j.jid.2019.05.009
DO - 10.1016/j.jid.2019.05.009
M3 - Article
C2 - 31152755
AN - SCOPUS:85070689817
SN - 0022-202X
VL - 139
SP - 2477
EP - 2487
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 12
ER -