Mitchell Kronenberg

Last updated
Mitchell Kronenberg
Born (1951-12-12) December 12, 1951 (age 71)
Alma mater Columbia University
California Institute of Technology
Scientific career
Fields Immunology
Institutions University of California, Los Angeles
La Jolla Institute for Immunology

Mitchell Kronenberg (born December 12, 1951) is an American immunologist and the chief scientific officer at La Jolla Institute for Immunology. He served as president of the institute from 2003 to 2021. [1]  

Contents

Education

Kronenberg received his Bachelor of Science degree from Columbia University in 1973 and a Ph.D. from the California Institute of Technology, [2] where he stayed on to complete postdoctoral work in the laboratory of Leroy Hood.

Scientific career

In 1986, Kronenberg joined the faculty at UCLA, where he rose through the ranks and was promoted to full professor in 1997. In 1997, he moved to La Jolla Institute for Immunology (LJI) to head the Division of Developmental Immunology. He was appointed president and chief scientific officer of LJI in 2003. [3]

Kronenberg is an adjunct professor of Biology [4] at UC San Diego and co-directs the Program in Immunology, [5] a collaborative effort between La Jolla Institute and UC San Diego. During his leadership, LJI formalized its ties with UC San Diego, [6] maintained its relationship with Kyowa Kirin, expanded its core facilities and technologic prowess, increased its budget four-fold and grew in reputation. [7]

From 2009 to 2015, he was also the secretary-treasurer of the American Association of Immunologists. [8] He advises many organizations, including the National Cancer Institute on the Board of Scientific Counselors. 

Research

The Kronenberg lab focuses on understanding innate-like lymphocytes, mainly natural killer T (NKT) cells, a subset of T cells that recognizes glycolipids and is involved in a variety of immune responses including autoimmune, anti-tumoral responses and antimicrobial responses. Kronenberg also has research in mucosal immunology and on the development of inflammatory bowel diseases.

Kronenberg's work had a major impact in defining how glycolipid antigens are taken into cells and processed in lysosomes [9] and unraveled the intracellular traffic of CD1d, [10] which is the MHC class I molecule that presents lipid antigens. He has led the field in defining microbial antigens from environmental bacteria [11] and from pathogenic microbes for mouse and human NKT cells, [12] [13] characterizing the biochemistry of antigen recognition, and has shown that NKT cells are protective in Lyme disease [14] and pneumonia. [15] [13] In the mucosal immune system, major findings from the Kronenberg laboratory have identified functions of another MHC class I antigen presenting molecule expressed in intestine epithelium, the Thymus Leukemia antigen. [16] His work has determined how the balance of regulatory versus pro-inflammatory responses occurs, with breakthroughs in understanding the roles of retinoic acid [17] and IL-10. Recently, they demonstrated that HVEM, a TNF receptor homolog, has enormous influence on the mucosal immune response by triggering protective innate anti-microbial responses against important pathogens by innate lymphoid cells type 3 (ILC3) [18] and epithelial cells in the intestine. [19]

Awards

Kronenberg was elected a fellow of the American Association for the Advancement of Science in 2015. [8] He received the Distinguished Service Award from the American Association of Immunologists (AAI) and was elected a Distinguished Fellow of the AAI in 2019. [8]

Personal life

Kronenberg is married to Hilde Cheroutre, also a professor at La Jolla Institute and they have collaborated on a number of studies. [20] [21]

Related Research Articles

<span class="mw-page-title-main">T cell</span> White blood cells of the immune system

T cells are one of the important types of white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface.

<span class="mw-page-title-main">Polly Matzinger</span> French-born American immunologist

Polly Celine Eveline Matzinger is a French-born immunologist who proposed the danger model theory of how the immune system works.

Pathogen-associated molecular patterns (PAMPs) are small molecular motifs conserved within a class of microbes, but not present in the host. They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) in both plants and animals. This allows the innate immune system to recognize pathogens and thus, protect the host from infection.

Gut-associated lymphoid tissue (GALT) is a component of the mucosa-associated lymphoid tissue (MALT) which works in the immune system to protect the body from invasion in the gut.

<span class="mw-page-title-main">Intraepithelial lymphocyte</span>

Intraepithelial lymphocytes (IEL) are lymphocytes found in the epithelial layer of mammalian mucosal linings, such as the gastrointestinal (GI) tract and reproductive tract. However, unlike other T cells, IELs do not need priming. Upon encountering antigens, they immediately release cytokines and cause killing of infected target cells. In the GI tract, they are components of gut-associated lymphoid tissue (GALT).

A tetramer assay is a procedure that uses tetrameric proteins to detect and quantify T cells that are specific for a given antigen within a blood sample. The tetramers used in the assay are made up of four major histocompatibility complex (MHC) molecules, which are found on the surface of most cells in the body. MHC molecules present peptides to T-cells as a way to communicate the presence of viruses, bacteria, cancerous mutations, or other antigens in a cell. If a T-cell's receptor matches the peptide being presented by an MHC molecule, an immune response is triggered. Thus, MHC tetramers that are bioengineered to present a specific peptide can be used to find T-cells with receptors that match that peptide. The tetramers are labeled with a fluorophore, allowing tetramer-bound T-cells to be analyzed with flow cytometry. Quantification and sorting of T-cells by flow cytometry enables researchers to investigate immune response to viral infection and vaccine administration as well as functionality of antigen-specific T-cells. Generally, if a person's immune system has encountered a pathogen, the individual will possess T cells with specificity toward some peptide on that pathogen. Hence, if a tetramer stain specific for a pathogenic peptide results in a positive signal, this may indicate that the person's immune system has encountered and built a response to that pathogen.

Charles Alderson Janeway, Jr. (1943–2003) was a noted immunologist who helped create the modern field of innate immunity. A member of the National Academy of Sciences, he held a faculty position at Yale University's Medical School and was an Howard Hughes Medical Institute Investigator.

<span class="mw-page-title-main">La Jolla Institute for Immunology</span>

La Jolla Institute for Immunology is a non-profit research organization located in La Jolla, San Diego, California. It is located in UC San Diego’s Research Park. The institute researches immunology and immune system diseases. The institute employs 220 M.D.s and Ph.D.s, including 23 faculty members and more than 450 employees. Dr. Mitchell Kronenberg has served as its president and scientific director since 2003. The institute was founded in 1988.

<span class="mw-page-title-main">Microbial symbiosis and immunity</span>

Long-term close-knit interactions between symbiotic microbes and their host can alter host immune system responses to other microorganisms, including pathogens, and are required to maintain proper homeostasis. The immune system is a host defense system consisting of anatomical physical barriers as well as physiological and cellular responses, which protect the host against harmful microorganisms while limiting host responses to harmless symbionts. Humans are home to 1013 to 1014 bacteria, roughly equivalent to the number of human cells, and while these bacteria can be pathogenic to their host most of them are mutually beneficial to both the host and bacteria.

<span class="mw-page-title-main">Mucosal immunology</span> Field of study

Mucosal immunology is the study of immune system responses that occur at mucosal membranes of the intestines, the urogenital tract, and the respiratory system. The mucous membranes are in constant contact with microorganisms, food, and inhaled antigens. In healthy states, the mucosal immune system protects the organism against infectious pathogens and maintains a tolerance towards non-harmful commensal microbes and benign environmental substances. Disruption of this balance between tolerance and deprivation of pathogens can lead to pathological conditions such as food allergies, irritable bowel syndrome, susceptibility to infections, and more.

Natural killer T (NKT) cells are a heterogeneous group of T cells that share properties of both T cells and natural killer cells. Many of these cells recognize the non-polymorphic CD1d molecule, an antigen-presenting molecule that binds self and foreign lipids and glycolipids. They constitute only approximately 1% of all peripheral blood T cells. Natural killer T cells should neither be confused with natural killer cells nor killer T cells.

Mucosal-associated invariant T cells make up a subset of T cells in the immune system that display innate, effector-like qualities. In humans, MAIT cells are found in the blood, liver, lungs, and mucosa, defending against microbial activity and infection. The MHC class I-like protein, MR1, is responsible for presenting bacterially-produced vitamin B2 and B9 metabolites to MAIT cells. After the presentation of foreign antigen by MR1, MAIT cells secrete pro-inflammatory cytokines and are capable of lysing bacterially-infected cells. MAIT cells can also be activated through MR1-independent signaling. In addition to possessing innate-like functions, this T cell subset supports the adaptive immune response and has a memory-like phenotype. Furthermore, MAIT cells are thought to play a role in autoimmune diseases, such as multiple sclerosis, arthritis and inflammatory bowel disease, although definitive evidence is yet to be published.

<span class="mw-page-title-main">Akiko Iwasaki</span> Immunobiologist

Akiko Iwasaki is a Sterling Professor of Immunobiology and Molecular, Cellular and Developmental Biology at Yale University. She is also a principal investigator at the Howard Hughes Medical Institute. Her research interests include innate immunity, autophagy, inflammasomes, sexually transmitted infections, herpes simplex virus, human papillomavirus, respiratory virus infections, influenza infection, T cell immunity, commensal bacteria, COVID-19 and Long COVID.

<span class="mw-page-title-main">Type 3 innate lymphoid cells</span>

Type 3 innate lymphoid cells (ILC3) are immune cells from the lymphoid lineage that are part of the innate immune system. These cells participate in innate mechanisms on mucous membranes, contributing to tissue homeostasis, host-commensal mutualism and pathogen clearance. They are part of a heterogeneous group of innate lymphoid cells, which is traditionally divided into three subsets based on their expression of master transcription factors as well as secreted effector cytokines - ILC1, ILC2 and ILC3.

Seung-Yong Seong is a South Korean immunologist and microbiologist known for his study of innate immune system response and his development of the damage-associated molecular pattern (DAMP) model of immune response initiation in collaboration with Polly Matzinger. Seong is also known for his research on the bacterium Orientia tsutsugamushi and his research on immunological adjuvant when he was a student. Since 2013 he has served as Director of the Wide River Institute of Immunology – Seoul National University in conjunction with his Professor position in the Microbiology and Immunology department of Seoul National University College of Medicine. In 2012, he became Editor in Chief of the World Journal of Immunology.

α-Galactosylceramide is a synthetic glycolipid derived from structure-activity relationship studies of galactosylceramides isolated from the marine sponge Agelas mauritianus. α-GalCer is a strong immunostimulant and shows potent anti-tumour activity in many in vivo models.

<span class="mw-page-title-main">Alessandro Sette</span> Italian immunologist (born 1960)

Alessandro Sette is an Italian immunologist. He was born on August 11, 1960, in Rome, Italy, to Pietro Sette, a prominent Italian businessman and politician, and Renata Sette. Sette is a professor at La Jolla Institute for Immunology (LJI). He is an adjunct professor at the University of California, San Diego. Sette studies the specific epitopes that the immune system recognizes in cancer, autoimmunity, allergy, and infectious diseases.

Shane Patrick Crotty is a professor of immunology in the Center for Infectious Disease and Vaccine Research at La Jolla Institute for Immunology.

Wendy Havran was an American immunologist at the Scripps Research Institute. She specialized in T cells, showing that they are scarce in certain areas of the body.

Cd1-restricted T cells are part of the unconventional T cell family, they are stimulated by exposure to CD1+ antigen presenting cells (APCs). Many CD1-restricted T cells are rapidly stimulated to carry out helper and effector functions upon interaction with CD1-expressing antigen-presenting cells. CD1-restricted T cells regulate host defence, antitumor immunity and the balance between tolerance and autoimmunity.

References

  1. ↑ Lu, Jamie (September 25, 2021). "La Jolla Institute for Immunology celebrates new president". Del Mar Times. Retrieved 2022-06-25.
  2. ↑ "Thank You to Our FY21 Donors". Columbia College Today. 2021-08-30. Retrieved 2022-08-13.
  3. ↑ "Mitchell Kronenberg, Ph.D." La Jolla Institute for Immunology. Retrieved 2022-06-25.
  4. ↑ "Mitchell Kronenberg". biology.ucsd.edu. Retrieved 2022-06-16.
  5. ↑ "Leadership". immunology.ucsd.edu. Retrieved 2022-06-16.
  6. ↑ Robbins, Gary (July 25, 2015). "Institute spurns USC, chooses UC San Diego". San Diego Union-Tribune. Retrieved 2022-06-25.
  7. ↑ "Xconomy: La Jolla Immunology Institute Agrees to Formal Ties with UCSD". Xconomy. 2015-07-29. Retrieved 2022-06-25.
  8. 1 2 3 "Mitchell Kronenberg, Ph.D." The American Association of Immunologists. Retrieved June 25, 2022.
  9. ↑ Prigozy, T. I.; Naidenko, O.; Qasba, P.; Elewaut, D.; Brossay, L.; Khurana, A.; Natori, T.; Koezuka, Y.; Kulkarni, A.; Kronenberg, M. (2001-01-26). "Glycolipid antigen processing for presentation by CD1d molecules". Science. 291 (5504): 664–667. doi:10.1126/science.291.5504.664. ISSN   0036-8075. PMID   11158680.
  10. ↑ Chandra, S.; Gray, J.; Kiosses, W.B.; Khurana, K.; Hitomi, K.; Crosby, C.; Chawla, A.; Fu, Z.; Zhao, M.; Veerapen, N.; Richardson, S.K. (2018). "Mrp1 is involved in lipid presentation and iNKT cell activation by Streptococcus pneumoniae". Nature Communications. 9 (1): 4279. doi:10.1038/s41467-018-06646-8. PMC   6189046 . PMID   30323255.
  11. ↑ Kinjo, Yuki; Wu, Douglass; Kim, Gisen; Xing, Guo-Wen; Poles, Michael A.; Ho, David D.; Tsuji, Moriya; Kawahara, Kazuyoshi; Wong, Chi-Huey; Kronenberg, Mitchell (2005-03-24). "Recognition of bacterial glycosphingolipids by natural killer T cells". Nature. 434 (7032): 520–525. doi:10.1038/nature03407. ISSN   1476-4687. PMID   15791257. S2CID   4412869.
  12. ↑ Kinjo, Yuki; Tupin, Emmanuel; Wu, Douglass; Fujio, Masakazu; Garcia-Navarro, Raquel; Benhnia, Mohammed Rafii-El-Idrissi; Zajonc, Dirk M.; Ben-Menachem, Gil; Ainge, Gary D.; Painter, Gavin F.; Khurana, Archana (September 2006). "Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria". Nature Immunology. 7 (9): 978–986. doi:10.1038/ni1380. ISSN   1529-2908. PMID   16921381. S2CID   25895420.
  13. 1 2 Kinjo, Yuki; Illarionov, Petr; Vela, José Luis; Pei, Bo; Girardi, Enrico; Li, Xiangming; Li, Yali; Imamura, Masakazu; Kaneko, Yukihiro; Okawara, Akiko; Miyazaki, Yoshitsugu (2011-09-04). "Invariant natural killer T cells recognize glycolipids from pathogenic Gram-positive bacteria". Nature Immunology. 12 (10): 966–974. doi:10.1038/ni.2096. ISSN   1529-2916. PMC   3178673 . PMID   21892173.
  14. ↑ Tupin, Emmanuel; Benhnia, Mohammed Rafii-El-Idrissi; Kinjo, Yuki; Patsey, Rebeca; Lena, Christopher J.; Haller, Matthew C.; Caimano, Melissa J.; Imamura, Masakazu; Wong, Chi-Huey; Crotty, Shane; Radolf, Justin D. (2008-12-16). "NKT cells prevent chronic joint inflammation after infection with Borrelia burgdorferi". Proceedings of the National Academy of Sciences of the United States of America. 105 (50): 19863–19868. doi: 10.1073/pnas.0810519105 . ISSN   1091-6490. PMC   2604993 . PMID   19060201.
  15. ↑ Chandra, S.; Gray, J.; Kiosses, W.B.; Khurana, A.; Hitomi, K.; Crosby, C.; Chawla, A.; Fu, Z.; Zhao, M.; Veerapen, N.; Richardson, S.K. (2018). "Mrp1 is involved in lipid presentation and iNKT cell activation by Streptococcus pneumoniae". Nature Communications. 9 (1): 4279. doi:10.1038/s41467-018-06646-8. PMC   6189046 . PMID   30323255.
  16. ↑ Leishman, A. J.; Naidenko, O. V.; Attinger, A.; Koning, F.; Lena, C. J.; Xiong, Y.; Chang, H. C.; Reinherz, E.; Kronenberg, M.; Cheroutre, H. (2001-11-30). "T cell responses modulated through interaction between CD8alphaalpha and the nonclassical MHC class I molecule, TL". Science. 294 (5548): 1936–1939. doi:10.1126/science.1063564. ISSN   0036-8075. PMID   11729321. S2CID   86097219.
  17. ↑ Mucida, Daniel; Park, Yunji; Kim, Gisen; Turovskaya, Olga; Scott, Iain; Kronenberg, Mitchell; Cheroutre, Hilde (2007-07-13). "Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid". Science. 317 (5835): 256–260. doi: 10.1126/science.1145697 . ISSN   1095-9203. PMID   17569825. S2CID   24736012.
  18. ↑ Seo, Goo Young; Shui, Jr Wen; Takahashi, Daisuke; Song, Christina; Wang, Qingyang; Kim, Kenneth; Mikulski, Zbigniew; Chandra, Shilpi; Giles, Daniel A.; Zahner, Sonja; Kim, Pyeung Hyeun (2018-08-08). "LIGHT-HVEM Signaling in Innate Lymphoid Cell Subsets Protects Against Enteric Bacterial Infection". Cell Host and Microbe. 24 (2): 249–260.e4. doi: 10.1016/j.chom.2018.07.008 . ISSN   1931-3128. PMC   6132068 . PMID   30092201.
  19. ↑ Shui, Jr-Wen; Larange, Alexandre; Kim, Gisen; Vela, Jose Luis; Zahner, Sonja; Cheroutre, Hilde; Kronenberg, Mitchell (2012-08-09). "HVEM signalling at mucosal barriers provides host defence against pathogenic bacteria". Nature. 488 (7410): 222–225. doi:10.1038/nature11242. ISSN   1476-4687. PMC   3477500 . PMID   22801499.
  20. ↑ "On Campus at GCC". Glendale News-Press. August 21, 2000. Retrieved 2022-06-25.
  21. ↑ "De La Jolla Institute a Santa Comba". La Voz de Galicia (in Spanish). 2013-12-15. Retrieved 2022-06-25.
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