Katharina Lahl

Ragnar Söderbergforskare i medicin // År: 2015 //
Anslagsförvaltare: Lunds Universitet // Belopp: 8 000 000 kr

Min forskning

Dendritiska celler i virusinfektioner

Katharina Lahl studerar hur de så kallade dendritiska cellerna fungerar när slemhinnorna i tarmvägg och lunga attackeras av infektioner. Målet är att förstå hur slemhinnornas immunförsvar känner igen främmande ämnen och hur detta påverkar immunförsvarets reaktion.

Katharina Lahl studerar hur slemhinnornas immunsystem i tarmvägg och lunga känner igen främmande ämnen och hur detta påverkar immunsystemets svar. Främmande ämnen – såväl smittämnen och allergener som födoämnen och den naturliga bakteriefloran – kan aktivera slemhinnornas immunförsvar.  

I sin forskning undersöker Lahl vad som kännetecknar slemhinnornas så kallade dendritiska celler, och hur de sätter igång kroppens produktion av antikroppar som skyddar oss mot infektioner. Dendritiska celler har som uppgift att presentera främmande ämnen i kroppen för andra celler. På så sätt aktiverar de immunförsvaret.

Resultaten från studierna kan förhoppningsvis bidra till ökade kunskaper om allergiska sjukdomar och vacciners funktion.

 

Research

Dendritic cells (DCs) guide the key processes leading to immune activation and ultimate clearance of invaders. Different DC subsets differ in their capacity of inducing specific immune responses. This project aims to define the requirements for DC subsets in immune recognition of viruses at mucosal surfaces. We will focus on both the molecular requirements for DC subset development and function, and how they cooperate with each other as well as with adaptive immune cells to induce secretory IgA.

We will use two different viruses, intestine tropic Rotavirus and lung tropic Respiratory syncytial virus, as models for these two mucosal surfaces. Both are a huge burden on society by causing the death of thousands of infants each year and both are restricted to the organ they infect. There is need for better vaccines for both viruses. By analyzing the transcriptional landscape of DC subsets across organs and species, we will clarify the developmental and functional differences between DC subsets at mucosal surfaces vs systemic sites and the differences between humans and mice.

We will study the consequences of differential transcriptomics between DC subsets particularly on humoral immunity towards viruses. Since infection by both model viruses causes severe symptoms almost exclusively in neonates, we will put an emphasis on studying the peculiarities of the newborns’ immature immune system with regard to DC-mediated protection from mucosal viruses.

Publikationer i urval

Lahl, K., Sweere, J., Pan, J. and E.C. Butcher. Orphan chemoattractant receptor GPR15 mediates dendritic epidermal T cell recruitment to the skin. Eur J Immunol. 2014; 44(9):2577-81

Watchmaker, P.W.* , Lahl, K.* , Lee, M., Baumjohann, D., Morton, J., Kim, S.J., Zeng, R., Dent, A, Ansel, K.M., Diamond, B., Hadeiba, H. and E.C. Butcher. Comparative transcriptional and functional profiling defines conserved programs of intestinal DC differentiation in humans and mice. Nat. Immunology 2014; 15 (1), 98-108

Deal, E.M.* , Lahl, K.* , Narvaez, C.F., Butcher, E.C., H.B. Greenberg. Plasmacytoid dendritic cells promote rotavirus-induced human and murine B cell responses. JCI 2013; 123(6):2464-74 

Kim, J.# , Lahl, K.# , Loddenkemper, C., Hori, S., Rudensky, A., T. Sparwasser. Cutting edge: depletion of Foxp3+ cells leads to induction of autoimmunity by specific ablation of regulatory T cells in genetically targeted mice. JI 2009 183(9):5662-72

Lahl, K., Mayer, C., Bopp T., Huehn, J., Loddenkemper, C., Dornmair, K., Eberl, G., Geffers, R., Schmidt, E., Buer, J., T. Sparwasser. Nonfunctional regulatory T cells and defective control of TH2 cytokine production in natural scurfy mutant mice. JI 2009 183(12):7631-4

Heit, A.# , Gebhardt, F.# , Lahl, K.# , Neuenhahn, M., Schmitz, F., Wagner, H., Sparwasser, T., Busch, D., K. Kastenmueller. Circumvention of regulatory CD4+ T cell activity during crosspriming strongly enhances T cell-mediated immunity. EJI 2008 38:1585- 1597

Lahl, K., C. Loddenkemper, C. Drouin, J. Freyer, J. Arnason, G. Eberl, A. Hamann, H. Wagner, J. Huehn, T. Sparwasser. Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. J Exp Med 2007 22;204(1):57 

Zeng, R., Bscheider, M., Lahl, K., Lee, M., E. Butcher. Generation and transcriptional programming of intestinal dendritic cells: Essential role of retinoic acid. Mucosal Immunology (accepted)

Mayer, C.T., Lahl, K., Milanez-Almeida, P., Watts, D., Dittmer, U., Fyhrquist, N., Huehn, J., Kopf, M., Kretschmer, K., Rouse, B., T. Sparwasser. Advantages of Foxp3(+) regulatory T cell depletion using DEREG mice. Immun. Inflamm. Dis. 2014; 2(3):162-5

Puttur, F., Arnold-Schrauf, C., Lahl, K., Solmaz, G., Lindenberg, M., Mayer, C.T., Gohmert, M., Swallow, M., van Helt, C., Schmitt, H., Nitschke, L., Lambrecht, B.N., Lang, R., Messerle, M., T. Sparwasser. Absence of Siglec-H in MCMV infection elevates Interferon alpha production but does not enhance viral clearance. PLOS Pathogens 2013;9(9):e1003648

* equal contribution
 # shared first authorship