FOR2599Project 8

Control of high-affinity IgE responses to animal venoms by skin innate type 2 immunity

Axel Roers, Institute for Immunology, Medical Faculty Carl Gustav Carus, TU Dresden

Rolf Jessberger, Institute for Physiological Chemistry, Medical Faculty Carl Gustav Carus, TU Dresden

Skin is a barrier tissue that is the site of induction of important type 2 immune responses. Defects of the barrier function result in stress responses inducing local innate type 2 immunity that has the potential to cause a systemic adaptive type 2 bias and thereby not only atopic dermatitis but also allergy and asthma. Skin is also the tissue first exposed to a wide spectrum of animal venoms upon stings or bites which induce a local type 2 immune response and robust IgE responses that can provide protection or cause allergy.

We address how skin tissue mounts type 2 responses upon exposure to animal venoms through stings or bites of insects or reptiles. We hypothesize that the immediate tissue response to the venom and subsequent activation of dermal and LN type 2 cells instruct amounts and affinity of the anti-venom IgE produced and thereby determine a beneficial or potentially fatal outcome.

Selected publications

Roers group

Predicitive framework for macrophage activation, Sanin DE * , Ge Y , Marinkovic E , Kabat AM, Castoldi A, Caputa G., Grzes KM, Curtis JD , Willenborg S , Dichtl S , Reinhardt S, Dahl A , Pearce EL*  ,  Eming SA* , Gerbaulet A* , Roers A* , Murray P* and Pearce EJ*, bioRxiv (*corresponding authors, in press)

Muhandes L, Pippel M, Chapsa M, Behrendt R, Ge Y, Dahl A,Yi B, Dalpke A, Winkler S, Hiller M, Beissert S, Jessberger R, Fallon PG, Roers A. Filaggrin deficient mice have a lower threshold for cutaneous allergen sensitization but do not develop spontaneous skin inflammation or atopy, J Invest Dermatol. 2021 Apr 22:S0022-202X(21)01155-6.

Mast Cells Occupy Stable Clonal Territories in Adult Steady-State Skin. Weitzmann A, Naumann R, Dudeck A, Zerjatke T, Gerbaulet A, Roers A.J Invest Dermatol. 2020 Dec;140(12):2433-2441.e5.

The Generation of an Engineered Interleukin-10 Protein With Improved Stability and Biological Function. Minshawi F, Lanvermann S, McKenzie E, Jeffery R, Couper K, Papoutsopoulou S, Roers A, Muller W.Front Immunol. 2020 Aug 11;11:1794.

Ghouse SM, Polikarpova A, Muhandes L, Dudeck J, Tantcheva-Poór I, Hartmann K, Lesche M, Dahl A, Eming S, Müller W, Behrendt R, Roers A. Although Abundant in Tumor Tissue, Mast Cells Have No Effect on Immunological Micro-milieu or Growth of HPV-Induced or Transplanted Tumors. Cell Rep. 2018;22:27-35

Chmelar J, Chatzigeorgiou A, Chung KJ, Prucnal M, Voehringer D, Roers A, Chavakis T. No Role for Mast Cells in Obesity-Related Metabolic Dysregulation. Front Immunol. 2016;7:524.

Peschke K, Weitzmann A, Heger K, Behrendt R, Schubert N, Scholten J, Voehringer D, Hartmann K, Dudeck A, Schmidt-Supprian M, Roers A. I?B kinase 2 is essential for IgE-induced mast cell de novo cytokine production but not for degranulation. Cell Rep. 2014;8:1300-7.

Dudeck A, Dudeck J, Scholten J, Petzold A, Surianarayanan S, Köhler A, Peschke K, Vöhringer D, Waskow C, Krieg T, Müller W, Waisman A, Hartmann K, Gunzer M, Roers A. Mast cells are key promoters of contact allergy that mediate the adjuvant effects of haptens. Immunity 2011;34:973-84.

Scholten J, Hartmann K, Gerbaulet A, Krieg T, Müller W, Testa G, Roers A. Mast cell-specific Cre/loxP-mediated recombination in vivo. Transgenic Res. 2008;17:307-15.

Jessberger group

Control of GM-CSF-Dependent Dendritic Cell Differentiation and Maturation by DEF6 and SWAP-70. Popović J, Wellstein I, Pernis A, Jessberger R, Ocaña-Morgner C.J Immunol. 2020 Sep 1;205(5):1306-1317

Regulation of the pleiotropic effects of tissue-resident mast cells. Huber M, Cato ACB, Ainooson GK, Freichel M, Tsvilovskyy V, Jessberger R, Riedlinger E, Sommerhoff CP, Bischoff SC.J Allergy Clin Immunol. 2019 Oct;144(4S):S31-S45.

Tolerogenic versus Immunogenic Lipidomic Profiles of CD11c+ Immune Cells and Control of Immunogenic Dendritic Cell Ceramide Dynamics. Ocaña-Morgner C, Sales S, Rothe M, Shevchenko A, Jessberger R.J Immunol. 2017 Jun 1;198(11):4360-4372.

Stage-specific binding profiles of cohesin in resting and activated B lymphocytes suggest a role for cohesin in immunoglobulin class switching and maturation. Günal-Sadık G, Paszkowski-Rogacz M, Singaravelu K, Beyer A, Buchholz F, Jessberger R.PLoS One. 2014 Nov 6;9(11):e111748

SWAP-70 restricts spontaneous maturation of dendritic cells. Ocaña-Morgner C, Götz A, Wahren C, Jessberger R.J Immunol. 2013 Jun 1;190(11):5545-58.

Control of the STAT6-BCL6 antagonism by SWAP-70 determines IgE production. Audzevich T, Pearce G, Breucha M, Günal G, Jessberger R.J Immunol. 2013 May 15;190(10):4946-55